Abstract: This paper describes the synthesis and antitumor activity of4-acylthiol - 4 - deoxy - 4 '- demethylepipodophyllotoxin analogues. 4- Mercapto-4- deoxy- 4'- demethylepipodophyllotoxin prepared from 4' - demethylepipodo-phyllo-toxin with H₂S in the presence of BF₃ ·Et₂0, was acylated with different acidsusing diethyl cyanophosphonate and thus, corresponding 4-acylthiol- 4-deoxy-4'-demethyl epipodophyllotoxin analogues were synthesized. These compounds were screenedin L1210 leukemia and KB cells, and one compound has activity similar to etoposide,and others were generally weaker than etoposide and corresponding 4-acylamido-4-deoxy-4' - demethylepipodophyllotoxin analogues.