diff --git a/mypyc/irbuild/builder.py b/mypyc/irbuild/builder.py
index 587be873a46d..39e2c6aa5181 100644
--- a/mypyc/irbuild/builder.py
+++ b/mypyc/irbuild/builder.py
@@ -62,6 +62,7 @@
     BITMAP_BITS,
     EXT_SUFFIX,
     GENERATOR_ATTRIBUTE_PREFIX,
+    IS_FREE_THREADED,
     MODULE_PREFIX,
     SELF_NAME,
     TEMP_ATTR_NAME,
@@ -146,7 +147,12 @@
 from mypyc.options import CompilerOptions
 from mypyc.primitives.dict_ops import dict_get_item_op, dict_set_item_op
 from mypyc.primitives.generic_ops import iter_op, next_op, py_setattr_op
-from mypyc.primitives.list_ops import list_get_item_unsafe_op, list_pop_last, to_list
+from mypyc.primitives.list_ops import (
+    list_get_item_int64_op,
+    list_get_item_unsafe_op,
+    list_pop_last,
+    to_list,
+)
 from mypyc.primitives.misc_ops import (
     check_unpack_count_op,
     get_module_dict_op,
@@ -893,7 +899,10 @@ def process_sequence_assignment(
             index: Value
             if is_list_rprimitive(rvalue.type):
                 index = Integer(i, c_pyssize_t_rprimitive)
-                item_value = self.primitive_op(list_get_item_unsafe_op, [rvalue, index], line)
+                if not IS_FREE_THREADED:
+                    item_value = self.primitive_op(list_get_item_unsafe_op, [rvalue, index], line)
+                else:
+                    item_value = self.primitive_op(list_get_item_int64_op, [rvalue, index], line)
             elif is_tuple_rprimitive(rvalue.type):
                 index = Integer(i, c_pyssize_t_rprimitive)
                 item_value = self.call_c(tuple_get_item_unsafe_op, [rvalue, index], line)
diff --git a/mypyc/primitives/list_ops.py b/mypyc/primitives/list_ops.py
index 25c9cd4b4c31..8af7e9e71df7 100644
--- a/mypyc/primitives/list_ops.py
+++ b/mypyc/primitives/list_ops.py
@@ -110,7 +110,7 @@
 )
 
 # Version with native int index
-method_op(
+list_get_item_int64_op = method_op(
     name="__getitem__",
     arg_types=[list_rprimitive, int64_rprimitive],
     return_type=object_rprimitive,
diff --git a/mypyc/test-data/irbuild-statements.test b/mypyc/test-data/irbuild-statements.test
index df7eb5fc7449..8199cfdaa699 100644
--- a/mypyc/test-data/irbuild-statements.test
+++ b/mypyc/test-data/irbuild-statements.test
@@ -575,7 +575,7 @@ L0:
     z = r6
     return 1
 
-[case testMultipleAssignmentUnpackFromSequence]
+[case testMultipleAssignmentUnpackFromSequence_withgil]
 from typing import List, Tuple
 
 def f(l: List[int], t: Tuple[int, ...]) -> None:
@@ -612,6 +612,43 @@ L0:
     y = r9
     return 1
 
+[case testMultipleAssignmentUnpackFromSequence_nogil]
+from typing import List, Tuple
+
+def f(l: List[int], t: Tuple[int, ...]) -> None:
+    x: object
+    y: int
+    x, y = l
+    x, y = t
+[out]
+def f(l, t):
+    l :: list
+    t :: tuple
+    r0 :: i32
+    r1 :: bit
+    r2, r3, x :: object
+    r4, y :: int
+    r5 :: i32
+    r6 :: bit
+    r7, r8 :: object
+    r9 :: int
+L0:
+    r0 = CPySequence_CheckUnpackCount(l, 2)
+    r1 = r0 >= 0 :: signed
+    r2 = CPyList_GetItemInt64(l, 0)
+    r3 = CPyList_GetItemInt64(l, 1)
+    x = r2
+    r4 = unbox(int, r3)
+    y = r4
+    r5 = CPySequence_CheckUnpackCount(t, 2)
+    r6 = r5 >= 0 :: signed
+    r7 = CPySequenceTuple_GetItemUnsafe(t, 0)
+    r8 = CPySequenceTuple_GetItemUnsafe(t, 1)
+    x = r7
+    r9 = unbox(int, r8)
+    y = r9
+    return 1
+
 [case testAssert]
 from typing import Optional