BUG: empty_frame[tuple] = values corrupting frame

doc/source/whatsnew/v3.0.0.rst

@@ -1132,6 +1132,7 @@ Indexing
 ^^^^^^^^
 - Bug in :meth:`DataFrame.__getitem__` returning modified columns when called with ``slice`` in Python 3.12 (:issue:`57500`)
 - Bug in :meth:`DataFrame.__getitem__` when slicing a :class:`DataFrame` with many rows raised an ``OverflowError`` (:issue:`59531`)
+- Bug in :meth:`DataFrame.__setitem__` on an empty :class:`DataFrame` with a tuple corrupting the frame (:issue:`54385`)
 - Bug in :meth:`DataFrame.from_records` throwing a ``ValueError`` when passed an empty list in ``index`` (:issue:`58594`)
 - Bug in :meth:`DataFrame.loc` and :meth:`DataFrame.iloc` returning incorrect dtype when selecting from a :class:`DataFrame` with mixed data types. (:issue:`60600`)
 - Bug in :meth:`DataFrame.loc` with inconsistent behavior of loc-set with 2 given indexes to Series (:issue:`59933`)

pandas/core/indexes/base.py

@@ -5193,7 +5193,9 @@ def _validate_fill_value(self, value):
         """
         dtype = self.dtype
         if isinstance(dtype, np.dtype) and dtype.kind not in "mM":
-            # return np_can_hold_element(dtype, value)
+            if isinstance(value, tuple) and dtype != object:
+                # GH#54385
+                raise TypeError
             try:
                 return np_can_hold_element(dtype, value)
             except LossySetitemError as err:
@@ -6357,6 +6359,10 @@ def _find_common_type_compat(self, target) -> DtypeObj:
         """
         target_dtype, _ = infer_dtype_from(target)
 
+        if isinstance(target, tuple):
+            # GH#54385
+            return np.dtype(object)
+
         if using_string_dtype():
             # special case: if left or right is a zero-length RangeIndex or
             # Index[object], those can be created by the default empty constructors

pandas/tests/frame/indexing/test_setitem.py

@@ -1002,6 +1002,15 @@ def test_loc_expansion_with_timedelta_type(self):
         )
         tm.assert_frame_equal(result, expected)
 
+    def test_setitem_tuple_key_in_empty_frame(self):
+        # GH#54385
+        df = DataFrame()
+        df[(0, 0)] = [1, 2, 3]
+
+        cols = Index([(0, 0)], tupleize_cols=False)
+        expected = DataFrame({(0, 0): [1, 2, 3]}, columns=cols)
+        tm.assert_frame_equal(df, expected)
+
 
 class TestDataFrameSetItemSlicing:
     def test_setitem_slice_position(self):