diff --git a/src/box/box.cc b/src/box/box.cc
index 7041d647e12d1d12f41091fdac24aa90b9e42f36..be23903350740fba814babc00df7a9db1b8ec0d2 100644
--- a/src/box/box.cc
+++ b/src/box/box.cc
@@ -471,22 +471,31 @@ box_check_replication_sync_timeout(void)
 	return timeout;
 }
 
+static inline void
+box_check_uuid(struct tt_uuid *uuid, const char *name)
+{
+	*uuid = uuid_nil;
+	const char *uuid_str = cfg_gets(name);
+	if (uuid_str == NULL)
+		return;
+	if (tt_uuid_from_string(uuid_str, uuid) != 0)
+		tnt_raise(ClientError, ER_CFG, name, uuid_str);
+	if (tt_uuid_is_nil(uuid)) {
+		tnt_raise(ClientError, ER_CFG, name,
+			  tt_sprintf("nil UUID is reserved"));
+	}
+}
+
 static void
 box_check_instance_uuid(struct tt_uuid *uuid)
 {
-	*uuid = uuid_nil;
-	const char *uuid_str = cfg_gets("instance_uuid");
-	if (uuid_str != NULL && tt_uuid_from_string(uuid_str, uuid) != 0)
-		tnt_raise(ClientError, ER_CFG, "instance_uuid", uuid_str);
+	box_check_uuid(uuid, "instance_uuid");
 }
 
 static void
 box_check_replicaset_uuid(struct tt_uuid *uuid)
 {
-	*uuid = uuid_nil;
-	const char *uuid_str = cfg_gets("replicaset_uuid");
-	if (uuid_str != NULL && tt_uuid_from_string(uuid_str, uuid) != 0)
-		tnt_raise(ClientError, ER_CFG, "replicaset_uuid", uuid_str);
+	box_check_uuid(uuid, "replicaset_uuid");
 }
 
 static enum wal_mode
diff --git a/test/app-tap/cfg.test.lua b/test/app-tap/cfg.test.lua
index a2cbed8ddedf8dcfaae039ca141d81db16fb7393..ba6b735abb5a0082aeda26ec8713df947414c3d6 100755
--- a/test/app-tap/cfg.test.lua
+++ b/test/app-tap/cfg.test.lua
@@ -3,7 +3,17 @@ local fiber = require('fiber')
 local tap = require('tap')
 local test = tap.test("cfg")
 
-test:plan(9)
+test:plan(11)
+
+--
+-- gh-4282: box.cfg should not allow nor just ignore nil UUID.
+-- It is a special reserved value.
+--
+local nil_uuid = '00000000-0000-0000-0000-000000000000'
+local ok = pcall(box.cfg, {instance_uuid = nil_uuid})
+test:ok(not ok, 'nil instance UUID is not allowed')
+ok, err = pcall(box.cfg, {replicaset_uuid = nil_uuid})
+test:ok(not ok, 'nil replicaset UUID is not allowed')
 
 test:is(type(box.ctl), "table", "box.ctl is available before box.cfg")
 test:is(type(box.ctl.wait_ro), "function", "box.ctl.wait_ro is available")