diff --git a/doc/source/whatsnew/v1.4.0.rst b/doc/source/whatsnew/v1.4.0.rst
index 4c3e53ddcfa26..029fb187740b3 100644
--- a/doc/source/whatsnew/v1.4.0.rst
+++ b/doc/source/whatsnew/v1.4.0.rst
@@ -815,6 +815,7 @@ Indexing
 - Fixed regression where a single column ``np.matrix`` was no longer coerced to a 1d ``np.ndarray`` when added to a :class:`DataFrame` (:issue:`42376`)
 - Bug in :meth:`Series.__getitem__` with a :class:`CategoricalIndex` of integers treating lists of integers as positional indexers, inconsistent with the behavior with a single scalar integer (:issue:`15470`, :issue:`14865`)
 - Bug in :meth:`Series.__setitem__` when setting floats or integers into integer-dtype series failing to upcast when necessary to retain precision (:issue:`45121`)
+- Bug in :meth:`DataFrame.iloc.__setitem__` ignores axis argument (:issue:`45032`)
 -
 
 Missing
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 8f776d280afad..0ac44ba53ae05 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -1540,7 +1540,11 @@ def _convert_to_indexer(self, key, axis: int):
     def _get_setitem_indexer(self, key):
         # GH#32257 Fall through to let numpy do validation
         if is_iterator(key):
-            return list(key)
+            key = list(key)
+
+        if self.axis is not None:
+            return self._convert_tuple(key)
+
         return key
 
     # -------------------------------------------------------------------
diff --git a/pandas/tests/indexing/test_iloc.py b/pandas/tests/indexing/test_iloc.py
index 17a990a6c7a38..ee9d276925d41 100644
--- a/pandas/tests/indexing/test_iloc.py
+++ b/pandas/tests/indexing/test_iloc.py
@@ -444,6 +444,18 @@ def test_iloc_setitem(self):
         expected = Series([0, 1, 0], index=[4, 5, 6])
         tm.assert_series_equal(s, expected)
 
+    def test_iloc_setitem_axis_argument(self):
+        # GH45032
+        df = DataFrame([[6, "c", 10], [7, "d", 11], [8, "e", 12]])
+        expected = DataFrame([[6, "c", 10], [7, "d", 11], [5, 5, 5]])
+        df.iloc(axis=0)[2] = 5
+        tm.assert_frame_equal(df, expected)
+
+        df = DataFrame([[6, "c", 10], [7, "d", 11], [8, "e", 12]])
+        expected = DataFrame([[6, "c", 5], [7, "d", 5], [8, "e", 5]])
+        df.iloc(axis=1)[2] = 5
+        tm.assert_frame_equal(df, expected)
+
     def test_iloc_setitem_list(self):
 
         # setitem with an iloc list