diff --git a/lisp/emacs-lisp/seq.el b/lisp/emacs-lisp/seq.el
index f2f7d677e88..7aa5684cfd1 100644
--- a/lisp/emacs-lisp/seq.el
+++ b/lisp/emacs-lisp/seq.el
@@ -468,6 +468,7 @@ Equality is defined by TESTFN if non-nil or by `equal' if nil."
               (seq-reverse sequence1)
               '()))
 
+;;;###autoload
 (cl-defgeneric seq-difference (sequence1 sequence2 &optional testfn)
   "Return a list of the elements that appear in SEQUENCE1 but not in SEQUENCE2.
 Equality is defined by TESTFN if non-nil or by `equal' if nil."
diff --git a/lisp/gnus/gnus-cite.el b/lisp/gnus/gnus-cite.el
index 1f564f192b0..4249b50b9ff 100644
--- a/lisp/gnus/gnus-cite.el
+++ b/lisp/gnus/gnus-cite.el
@@ -839,7 +839,7 @@ See also the documentation for `gnus-article-highlight-citation'."
 		 (setq current (car loop)
 		       loop (cdr loop))
 		 (setcdr current
-			 (gnus-set-difference (cdr current) numbers)))))))))
+                         (seq-difference (cdr current) numbers #'eq)))))))))
 
 (defun gnus-cite-parse-attributions ()
   (let (al-alist)
@@ -999,7 +999,7 @@ See also the documentation for `gnus-article-highlight-citation'."
 		    loop (cdr loop))
 	      (if (eq current best)
 		  ()
-		(setcdr current (gnus-set-difference (cdr current) numbers))
+                (setcdr current (seq-difference (cdr current) numbers #'eq))
 		(when (null (cdr current))
 		  (setq gnus-cite-loose-prefix-alist
 			(delq current gnus-cite-loose-prefix-alist)
diff --git a/lisp/gnus/gnus-range.el b/lisp/gnus/gnus-range.el
index 456209f3d9a..7d12ae9fdcc 100644
--- a/lisp/gnus/gnus-range.el
+++ b/lisp/gnus/gnus-range.el
@@ -42,13 +42,8 @@ If RANGE is a single range, return (RANGE).  Otherwise, return RANGE."
 
 (defun gnus-set-difference (list1 list2)
   "Return a list of elements of LIST1 that do not appear in LIST2."
-  (let ((hash2 (make-hash-table :test 'eq))
-        (result nil))
-    (dolist (elt list2) (puthash elt t hash2))
-    (dolist (elt list1)
-      (unless (gethash elt hash2)
-        (setq result (cons elt result))))
-    (nreverse result)))
+  (declare (obsolete seq-difference "28.1"))
+  (seq-difference list1 list2 #'eq))
 
 (defun gnus-range-nconcat (&rest ranges)
   "Return a range comprising all the RANGES, which are pre-sorted.
diff --git a/lisp/gnus/gnus-sum.el b/lisp/gnus/gnus-sum.el
index ac9317ef4e2..eeb5ac851ae 100644
--- a/lisp/gnus/gnus-sum.el
+++ b/lisp/gnus/gnus-sum.el
@@ -8569,8 +8569,9 @@ If UNREPLIED (the prefix), limit to unreplied articles."
   (interactive "P" gnus-summary-mode)
   (if unreplied
       (gnus-summary-limit
-       (gnus-set-difference gnus-newsgroup-articles
-	gnus-newsgroup-replied))
+       (seq-difference gnus-newsgroup-articles
+                       gnus-newsgroup-replied
+                       #'eq))
     (gnus-summary-limit gnus-newsgroup-replied))
   (gnus-summary-position-point))
 
diff --git a/lisp/gnus/gnus-uu.el b/lisp/gnus/gnus-uu.el
index 5cbe8495d31..ceb2ebcdcb1 100644
--- a/lisp/gnus/gnus-uu.el
+++ b/lisp/gnus/gnus-uu.el
@@ -579,7 +579,7 @@ didn't work, and overwrite existing files.  Otherwise, ask each time."
 (defun gnus-new-processable (unmarkp articles)
   (if unmarkp
       (nreverse (seq-intersection gnus-newsgroup-processable articles #'eq))
-    (gnus-set-difference articles gnus-newsgroup-processable)))
+    (seq-difference articles gnus-newsgroup-processable #'eq)))
 
 (defun gnus-uu-mark-by-regexp (regexp &optional unmark)
   "Set the process mark on articles whose subjects match REGEXP.
diff --git a/lisp/gnus/nnimap.el b/lisp/gnus/nnimap.el
index f06959f65d9..8990b2bebeb 100644
--- a/lisp/gnus/nnimap.el
+++ b/lisp/gnus/nnimap.el
@@ -1614,13 +1614,15 @@ If LIMIT, first try to limit the search to the N last articles."
 	      (setq start-article 1))
 	    (let* ((unread
 		    (gnus-compress-sequence
-		     (gnus-set-difference
-		      (gnus-set-difference
+                     (seq-difference
+                      (seq-difference
 		       existing
 		       (gnus-sorted-union
 			(cdr (assoc '%Seen flags))
-			(cdr (assoc '%Deleted flags))))
-		      (cdr (assoc '%Flagged flags)))))
+                        (cdr (assoc '%Deleted flags)))
+                       #'eq)
+                      (cdr (assoc '%Flagged flags))
+                      #'eq)))
 		   (read (gnus-range-difference
 			  (cons start-article high) unread)))
 	      (when (> start-article 1)
diff --git a/lisp/gnus/spam.el b/lisp/gnus/spam.el
index d00f0a60b66..3f978918b9a 100644
--- a/lisp/gnus/spam.el
+++ b/lisp/gnus/spam.el
@@ -710,16 +710,8 @@ finds ham or spam.")
 (defun spam-set-difference (list1 list2)
   "Return a set difference of LIST1 and LIST2.
 When either list is nil, the other is returned."
-  (if (and list1 list2)
-      ;; we have two non-nil lists
-      (progn
-        (dolist (item (append list1 list2))
-          (when (and (memq item list1) (memq item list2))
-            (setq list1 (delq item list1))
-            (setq list2 (delq item list2))))
-        (append list1 list2))
-    ;; if either of the lists was nil, return the other one
-    (if list1 list1 list2)))
+  (declare (obsolete seq-difference "28.1"))
+  (seq-difference list1 list2 #'eq))
 
 (defun spam-group-ham-mark-p (group mark &optional spam)
   "Checks if MARK is considered a ham mark in GROUP."
@@ -1327,7 +1319,7 @@ In the case of mover backends, checks the setting of
              (new-articles (spam-list-articles
                             gnus-newsgroup-articles
                             classification))
-             (changed-articles (spam-set-difference new-articles old-articles)))
+             (changed-articles (seq-difference new-articles old-articles #'eq)))
         ;; now that we have the changed articles, we go through the processors
         (dolist (backend (spam-backend-list))
           (let (unregister-list)