diff --git a/Lib/argparse.py b/Lib/argparse.py
index d8676118388..f365385a573 100644
--- a/Lib/argparse.py
+++ b/Lib/argparse.py
@@ -1967,7 +1967,7 @@ class ArgumentParser(_AttributeHolder, _ActionsContainer):
         for arg_string in arg_strings:
 
             # for regular arguments, just add them back into the list
-            if arg_string[0] not in self.fromfile_prefix_chars:
+            if not arg_string or arg_string[0] not in self.fromfile_prefix_chars:
                 new_arg_strings.append(arg_string)
 
             # replace arguments referencing files with the file content
diff --git a/Lib/test/test_argparse.py b/Lib/test/test_argparse.py
index 1a5f05e30b9..a7a4b005b00 100644
--- a/Lib/test/test_argparse.py
+++ b/Lib/test/test_argparse.py
@@ -1374,6 +1374,7 @@ class TestArgumentsFromFile(TempDirMixin, ParserTestCase):
         ('X @hello', NS(a=None, x='X', y=['hello world!'])),
         ('-a B @recursive Y Z', NS(a='A', x='hello world!', y=['Y', 'Z'])),
         ('X @recursive Z -a B', NS(a='B', x='X', y=['hello world!', 'Z'])),
+        (["-a", "", "X", "Y"], NS(a='', x='X', y=['Y'])),
     ]
 
 
diff --git a/Misc/NEWS b/Misc/NEWS
index 16ab20224c6..7a2eb5bb528 100644
--- a/Misc/NEWS
+++ b/Misc/NEWS
@@ -90,6 +90,8 @@ Core and Builtins
 Library
 -------
 
+- Issue #12353: argparse now correctly handles null argument values.
+
 - Issue #6493: An issue in ctypes on Windows that caused structure bitfields
   of type ctypes.c_uint32 and width 32 to incorrectly be set has been fixed.