diff --git a/python/cudf/cudf/core/dataframe.py b/python/cudf/cudf/core/dataframe.py
index b29089cb81a..8442cf05f01 100644
--- a/python/cudf/cudf/core/dataframe.py
+++ b/python/cudf/cudf/core/dataframe.py
@@ -405,12 +405,12 @@ def _setitem_tuple_arg(self, key, value):
                 value = as_column(value, length=length)
 
             new_col = cudf.Series(value, index=idx)
-            if not self._frame.empty:
+            if len(self._frame.index) != 0:
                 new_col = new_col._align_to_index(
                     self._frame.index, how="right"
                 )
 
-            if self._frame.empty:
+            if len(self._frame.index) == 0:
                 self._frame.index = (
                     idx if idx is not None else cudf.RangeIndex(len(new_col))
                 )
diff --git a/python/cudf/cudf/tests/test_indexing.py b/python/cudf/cudf/tests/test_indexing.py
index 5f5c4579e01..f49b9b02076 100644
--- a/python/cudf/cudf/tests/test_indexing.py
+++ b/python/cudf/cudf/tests/test_indexing.py
@@ -2255,3 +2255,12 @@ def test_scalar_loc_row_categoricalindex():
     result = df.loc["a"]
     expected = df.to_pandas().loc["a"]
     assert_eq(result, expected)
+
+
+def test_loc_setitem_empty_dataframe():
+    pdf = pd.DataFrame(index=["index_1", "index_2", "index_3"])
+    gdf = cudf.from_pandas(pdf)
+    pdf.loc[["index_1"], "new_col"] = "A"
+    gdf.loc[["index_1"], "new_col"] = "A"
+
+    assert_eq(pdf, gdf)