diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index ac3b5dcaf53ae..e46c729348d33 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -244,6 +244,7 @@ Indexing
 - Bug in :meth:`CategoricalIndex.get_indexer` failing to raise ``InvalidIndexError`` when non-unique (:issue:`38372`)
 - Bug in inserting many new columns into a :class:`DataFrame` causing incorrect subsequent indexing behavior (:issue:`38380`)
 - Bug in :meth:`DataFrame.loc`, :meth:`Series.loc`, :meth:`DataFrame.__getitem__` and :meth:`Series.__getitem__` returning incorrect elements for non-monotonic :class:`DatetimeIndex` for string slices (:issue:`33146`)
+- Bug in :meth:`DataFrame.__setitem__` raising ``ValueError`` with empty :class:`DataFrame` and specified columns for string indexer and non empty :class:`DataFrame` to set (:issue:`38831`)
 - Bug in :meth:`DataFrame.iloc.__setitem__` and :meth:`DataFrame.loc.__setitem__` with mixed dtypes when setting with a dictionary value (:issue:`38335`)
 - Bug in :meth:`DataFrame.loc` dropping levels of :class:`MultiIndex` when :class:`DataFrame` used as input has only one row (:issue:`10521`)
 -
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 1abbe37e67b09..aeae39094ba7c 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -3334,13 +3334,14 @@ def _ensure_valid_index(self, value):
         """
         # GH5632, make sure that we are a Series convertible
         if not len(self.index) and is_list_like(value) and len(value):
-            try:
-                value = Series(value)
-            except (ValueError, NotImplementedError, TypeError) as err:
-                raise ValueError(
-                    "Cannot set a frame with no defined index "
-                    "and a value that cannot be converted to a Series"
-                ) from err
+            if not isinstance(value, DataFrame):
+                try:
+                    value = Series(value)
+                except (ValueError, NotImplementedError, TypeError) as err:
+                    raise ValueError(
+                        "Cannot set a frame with no defined index "
+                        "and a value that cannot be converted to a Series"
+                    ) from err
 
             # GH31368 preserve name of index
             index_copy = value.index.copy()
diff --git a/pandas/tests/frame/indexing/test_setitem.py b/pandas/tests/frame/indexing/test_setitem.py
index 19d2f8301037a..28b1f02ff020c 100644
--- a/pandas/tests/frame/indexing/test_setitem.py
+++ b/pandas/tests/frame/indexing/test_setitem.py
@@ -338,6 +338,16 @@ def test_setitem_bool_with_numeric_index(self, dtype):
 
         tm.assert_index_equal(df.columns, expected_cols)
 
+    @pytest.mark.parametrize("indexer", ["B", ["B"]])
+    def test_setitem_frame_length_0_str_key(self, indexer):
+        # GH#38831
+        df = DataFrame(columns=["A", "B"])
+        other = DataFrame({"B": [1, 2]})
+        df[indexer] = other
+        expected = DataFrame({"A": [np.nan] * 2, "B": [1, 2]})
+        expected["A"] = expected["A"].astype("object")
+        tm.assert_frame_equal(df, expected)
+
 
 class TestDataFrameSetItemWithExpansion:
     def test_setitem_listlike_views(self):