diff --git a/doc/source/whatsnew/v2.2.0.rst b/doc/source/whatsnew/v2.2.0.rst
index 930e03ae7d75a..38a1c1511af73 100644
--- a/doc/source/whatsnew/v2.2.0.rst
+++ b/doc/source/whatsnew/v2.2.0.rst
@@ -292,6 +292,7 @@ Interval
 - Bug in :class:`Interval` ``__repr__`` not displaying UTC offsets for :class:`Timestamp` bounds. Additionally the hour, minute and second components will now be shown. (:issue:`55015`)
 - Bug in :meth:`IntervalIndex.get_indexer` with datetime or timedelta intervals incorrectly matching on integer targets (:issue:`47772`)
 - Bug in :meth:`IntervalIndex.get_indexer` with timezone-aware datetime intervals incorrectly matching on a sequence of timezone-naive targets (:issue:`47772`)
+- Bug in setting values on a :class:`Series` with an :class:`IntervalIndex` using a slice incorrectly raising (:issue:`54722`)
 -
 
 Indexing
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index 8703fef1e5940..e23887159c9c6 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -4204,15 +4204,9 @@ def _convert_slice_indexer(self, key: slice, kind: Literal["loc", "getitem"]):
                 self._validate_indexer("slice", key.step, "getitem")
                 return key
 
-        # convert the slice to an indexer here
-
-        # special case for interval_dtype bc we do not do partial-indexing
-        #  on integer Intervals when slicing
-        # TODO: write this in terms of e.g. should_partial_index?
-        ints_are_positional = self._should_fallback_to_positional or isinstance(
-            self.dtype, IntervalDtype
-        )
-        is_positional = is_index_slice and ints_are_positional
+        # convert the slice to an indexer here; checking that the user didn't
+        #  pass a positional slice to loc
+        is_positional = is_index_slice and self._should_fallback_to_positional
 
         # if we are mixed and have integers
         if is_positional:
diff --git a/pandas/tests/indexing/interval/test_interval.py b/pandas/tests/indexing/interval/test_interval.py
index 52a1d433712ff..ae25724972fde 100644
--- a/pandas/tests/indexing/interval/test_interval.py
+++ b/pandas/tests/indexing/interval/test_interval.py
@@ -134,6 +134,33 @@ def test_getitem_interval_with_nans(self, frame_or_series, indexer_sl):
 
         tm.assert_equal(result, expected)
 
+    def test_setitem_interval_with_slice(self):
+        # GH#54722
+        ii = IntervalIndex.from_breaks(range(4, 15))
+        ser = Series(range(10), index=ii)
+
+        orig = ser.copy()
+
+        # This should be a no-op (used to raise)
+        ser.loc[1:3] = 20
+        tm.assert_series_equal(ser, orig)
+
+        ser.loc[6:8] = 19
+        orig.iloc[1:4] = 19
+        tm.assert_series_equal(ser, orig)
+
+        ser2 = Series(range(5), index=ii[::2])
+        orig2 = ser2.copy()
+
+        # this used to raise
+        ser2.loc[6:8] = 22  # <- raises on main, sets on branch
+        orig2.iloc[1] = 22
+        tm.assert_series_equal(ser2, orig2)
+
+        ser2.loc[5:7] = 21
+        orig2.iloc[:2] = 21
+        tm.assert_series_equal(ser2, orig2)
+
 
 class TestIntervalIndexInsideMultiIndex:
     def test_mi_intervalindex_slicing_with_scalar(self):