diff --git a/Lib/tempfile.py b/Lib/tempfile.py
index 485038417c65c66..b5f799f8d685545 100644
--- a/Lib/tempfile.py
+++ b/Lib/tempfile.py
@@ -929,7 +929,8 @@ def __init__(self, suffix=None, prefix=None, dir=None,
     @classmethod
     def _rmtree(cls, name, ignore_errors=False, repeated=False):
         def onexc(func, path, exc):
-            if isinstance(exc, PermissionError):
+            # On DragonFly BSD, UF_NOUNLINK removal fails with EISDIR, not EPERM.
+            if isinstance(exc, (PermissionError, IsADirectoryError)):
                 if repeated and path == name:
                     if ignore_errors:
                         return
diff --git a/Misc/NEWS.d/next/Library/2026-07-21-01-13-39.gh-issue-154307.UNFKL4.rst b/Misc/NEWS.d/next/Library/2026-07-21-01-13-39.gh-issue-154307.UNFKL4.rst
new file mode 100644
index 000000000000000..fdba0c2940f0050
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2026-07-21-01-13-39.gh-issue-154307.UNFKL4.rst
@@ -0,0 +1,3 @@
+Fix :meth:`tempfile.TemporaryDirectory.cleanup` on DragonFly BSD, where removing
+a file with the ``UF_NOUNLINK`` flag failed with ``EISDIR`` instead of
+``EPERM``.