diff --git a/isort/core.py b/isort/core.py
index 78e0a1c03..c0bcd363a 100644
--- a/isort/core.py
+++ b/isort/core.py
@@ -9,7 +9,7 @@
 from . import output, parse
 from .exceptions import FileSkipComment
 from .format import format_natural, remove_whitespace
-from .settings import FILE_SKIP_RE
+from .settings import FILE_SKIP_COMMENTS
 
 CIMPORT_IDENTIFIERS = ("cimport ", "cimport*", "from.cimport")
 IMPORT_START_IDENTIFIERS = ("from ", "from.import", "import ", "import*") + CIMPORT_IDENTIFIERS
@@ -150,11 +150,12 @@ def process(
             if stripped_line and not line_separator:
                 line_separator = line[len(line.rstrip()) :].replace(" ", "").replace("\t", "")
 
-            if FILE_SKIP_RE.match(line):
-                if raise_on_skip:
-                    raise FileSkipComment("Passed in content")
-                isort_off = True
-                skip_file = True
+            for file_skip_comment in FILE_SKIP_COMMENTS:
+                if file_skip_comment in line:
+                    if raise_on_skip:
+                        raise FileSkipComment("Passed in content")
+                    isort_off = True
+                    skip_file = True
 
             if not in_quote:
                 if stripped_line == "# isort: off":
diff --git a/isort/settings.py b/isort/settings.py
index 29e17bcb7..d0060d056 100644
--- a/isort/settings.py
+++ b/isort/settings.py
@@ -54,7 +54,10 @@
 CYTHON_EXTENSIONS = frozenset({"pyx", "pxd"})
 SUPPORTED_EXTENSIONS = frozenset({"py", "pyi", *CYTHON_EXTENSIONS})
 BLOCKED_EXTENSIONS = frozenset({"pex"})
-FILE_SKIP_RE = re.compile(r"^#?\s?isort:\s?skip_file")
+FILE_SKIP_COMMENTS: Tuple[str, ...] = (
+    "isort:" + "skip_file",
+    "isort: " + "skip_file",
+)  # Concatenated to avoid this file being skipped
 MAX_CONFIG_SEARCH_DEPTH: int = 25  # The number of parent directories to for a config file within
 STOP_CONFIG_SEARCH_ON_DIRS: Tuple[str, ...] = (".git", ".hg")
 VALID_PY_TARGETS: Tuple[str, ...] = tuple(
diff --git a/tests/unit/test_isort.py b/tests/unit/test_isort.py
index 6f885581c..8a224ec8d 100644
--- a/tests/unit/test_isort.py
+++ b/tests/unit/test_isort.py
@@ -839,27 +839,6 @@ def test_skip_within_file() -> None:
         isort.code(test_input, known_third_party=["django"])
 
 
-def test_skip_comment_without_space_after_hash() -> None:
-    """Ensure skipping a whole file works."""
-    test_input = "#isort: skip_file\nimport django\nimport myproject\n"
-    with pytest.raises(FileSkipped):
-        isort.code(test_input, known_third_party=["django"])
-
-
-def test_skip_comment_with_multiline_comment() -> None:
-    """Ensure skipping a whole file works."""
-    test_input = '"""some comment\n\nisort: skip_file\nimport django\nimport myproject\n"""'
-    with pytest.raises(FileSkipped):
-        isort.code(test_input, known_third_party=["django"])
-
-
-def test_skip_comment_is_no_comment() -> None:
-    """Ensure skipping a whole file works."""
-    test_input = 'content = "# isort:skip_file"'
-    test_output = isort.code(test_input)
-    assert test_output == test_input
-
-
 def test_force_to_top() -> None:
     """Ensure forcing a single import to the top of its category works as expected."""
     test_input = "import lib6\nimport lib2\nimport lib5\nimport lib1\n"