From Sega Retro

The checksum is a rather simple security measure meant to prevent pirates from modifying the ROM image of a Sega Mega Drive game. It may also have been used for internal security, as a method to keep developers from making unauthorized changes to the code. At any rate, it has caused hackers incalculable headache until circumvention methods were discovered. Esrael wrote a program, ESE FixCheckSum, to correct the checksum. Emulators like Kega Fusion and Gens/GS provide an option to automatically correct checksums when a ROM is loaded.

The checksum is calculated by adding up every word from $200 to the end of the ROM. This is then compared against the value stored in the header, and if the values differ, the game displays a red screen and stops running. Most modern emulators fix the checksum automatically. The use of cheat devices such as a Game Genie may also trigger a checksum error, which can be mitigated by using a "master code".

Some games, such as Sonic & Knuckles, lack checksum checks, possibly because of the time required to check the entire ROM.