Thioxanthone derivatives were docked, synthesized, and tested for their anticancer activity. The molecular docking results showed that 1-hydroxythioxanthone, 2-chloro-1-hydroxythioxanthone, and 4-chloro-1-hydroxythioxanthone gave lower binding energy than erlotinib demonstrating that those thioxanthones have stronger interaction in the active site of EGFR protein. The addition of one hydroxyl and chloro groups on 1-hydroxythioxanthone greatly enhanced its inhibition in EGFR protein. All thioxanthone derivatives had hydrogen bonding interaction with MET769 residue. The in vitro anti-cancer assay against all cancer cells (T47D, HeLa, WiDr, A549) revealed that 2-chloro-1-hydroxythioxanthone and 4-chloro-1hydroxythioxanthone gave lower IC 50 than 1-hydroxythioxanthone due to the addition of one chloro substituent. Meanwhile, 1,3-dihydroxythioxanthone exhibited the strongest anticancer activity, as well as the highest selectivity index (3.22-19.55) among the other thioxanthones. Based on these findings, 1,3-dihydroxythioxanthone is a potential anticancer drug candidate for further development in the future.