The objective of study was to investigate the role of the polymorphisms and protein expression of CYP3A5 gene in the therapy and prognosis of acute leukemia (AL) patients, the polymorphisms of CYP3A5 gene and the expression of protein CYP3A5 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and immunohistochemistry method respectively. The results showed that there were three CYP3A5 genotypes in the 88 cases, namely CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 with frequencies of 26%, 50% and 24%, respectively. There were no significant differences in clinic data between the three groups, but the expressions of CYP3A5 of three groups were (36.6+/-19.2)%, (7.8+/-9.2)%, (0.5+/-0.9)%, the OS were (11.6+/-2.1) months, (30.5+/-12.2) months, (52.3+/-8.5) months, and the DFS were (7.5+/-1.8), (27+/-15.8), (52.3+/-8.1) months, respectively (p<0.05). It is concluded that the polymorphism of CYP3A5 gene is not related with the morbidity of AL, but closely associated with the expression of CYP3A5 in AL patients, and the latter are closely associated with the chemotherapeutic effect and prognosis. CYP3A5 genotype may be used as a new predictor to the chemotherapeutic effect and prognosis in AL cases.