Objective To investigate the correlation between the combination of smoking and the polymorphisms of cytochrome P450(CYP) 1A1-MspⅠ and glutathione S-transferase(GST) T1 genes and oral cancer. Methods The genetic polymorphisms of CYP1A1-MspⅠ and GSTT1 were detected by polymerase chain reaction(PCR) technique in peripheral blood leukocytes of 300 oral cancer cases and 300 non-cancer controls, and the correlation between smoking, the two metabolic enzymes genetic polymorphisms and oral cancer were analyzed. Results The frequencies of CYP1A1-MspⅠ(m2/m2) and GSTT1(-) were 38.33% and 69.33% in oral cancer cases and 21.00% and 44.33% in healthy controls respectively. Statistical tests showed significant difference in the frequencies between the two groups (P