Abstract: Objective :To investigate the expression of Topoisomerase Ilalpha (Topo Ⅱ a) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in acute leukemia (AL) patients and their correlation with clinical multidrug resistance. Methods :The expression of Topo Ⅱ a and DNA-PKcs were measured in bone marrow mononuclear cells of 62 AL patients by SP immunohistochemistry method. Results :1) The positive expression rate of Topo ! a in the treatment resistant group (33.3%)was significantly lower than that in the sensitive group (69.0%)(P<0.01). 2) The positive expression rate of DNA-PKcs in the treatment resistant group (51.5% "was significantly higher than that in the sensitive group (20.7%) (P<0.05). 3) In the positive expression cases of Topo Ⅱ a, the multidrug resistance rate in the DNA-PKcs positive expression group (61.5%) was significantly higher than that in DNA-PKcs negative expression group (16.7%) (P<0.05). In the negative expression cases of DNA-PKcs, the multidrug resistance rate in the Topo Ⅱ anegative expression group (61.9%) was significantly higher than that in Topo H a positive expression group (16.7%) (P<0.01). The lowest multidrug resistance rate was in the group of Topo ! a positive expression and DNA-PKcs negative expression (16.7%), the highest multidrug resistance rate was in the group of Topo Ⅱa negative expression and DNA-PKcs positive expression (90.0%) (P<0.001). There was no correlation between Topo Ⅱ a and DNA-PKcs expression. Conelusions :The lower expression of Topo Ⅱ aand the higher expression of DNA-PKcs have close relation with clinical multidrug resistance. The measurement of both Topo ! aand DNA-PKcs expression would predict drug resistance and prognosis for AL patients.