Abstract: Objective: To investigate the cytotoxic effect of manumycin combined individually with cisplatin (DDP), 5-fluorouracil (5-FU), pingyangmycin (PYM) and adriamycin (ADR) on carcinoma of the tongue. Methods: Cytotoxicity of manumycin was determined by MTT assay, and cytotoxicity of the other drugs alone was determined using the half concentration gradient design. The cytotoxicity of each drug administered in combination with manumycin was determined by the Chou TC lente-principle design. Results: Each drug applied singly showed an obvious cytotoxicity on Tca8113 tongue carcinoma cells. Combined administration of each drug with manumycin showed that with a dosage of corresponding ratio, manumycin produced an antagonism (3.75:1) as combined with Cisplatin, showed a combined mutual antagonism (0.75:1) with a lowconcentration when combined with 5-Fu and the synergism was overt as with a high concentration. The mutual synergism was shown after joint action of manumycin with Pingyangmycin (0.75:1) and with Adriamycin (30:1) (CI<1). Conclusion: The combination of manumycin with PYM and the combination of ADR, manumycin and 5-Fu at high concentration showed synergistic cytotoxicity to Tca8113 cells in vitro (CI<1).