The syntheses of N,S-substituted 4-chloro-2-mercapto-5-methylbenzenesulfonamide derivatives are described. The compounds 6-11, 14, 15 and 19-22 were tested for their in vitro anticancer activity against 9 human cancer cell lines. The most active compounds 6, 9 and 20 showed moderate cytotoxic activity and were approximately 5-fold less potent than cisplatin.