Acidic serine protease (ASP NJ ) purified from Neanthes japonica, is a fibrinolytic enzyme. Earthworm fibrinolytic enzyme has been recently reported with anti-tumor activity on human hepatoma cells. To investigate if ASP NJ play therapeutic effects on emergent blood cancer, acute promyelocytic leukemia (APL), we tested the effects of ASP NJ on APL cell line NB4. Our results showed that ASP NJ inhibited the growth of NB4 cells in a dose and time dependent manner. Cell apoptosis was induced by ASP NJ with obvious morphological changes. The sensitivity of cells to cytarabine and doxorubicin were greatly increased respectively by combination with ASP NJ . In contrast to inhibitory effects on NB4 cells, ASP NJ showed much less effect on normal human neutrophils survival. There were no effects of hemolysis and agglutination observed on normal human erythrocytes following ASP NJ treatment. Conclusively, our data suggest that ASP NJ may become a new candidate for leukemia therapeutic approaches.