with CR will relapse, with a long-term survival of less than 10%. In addition, treatment-related side effects are among the main factors limiting the clinical efficacy for AML treatment. It is of great practical significance to explore safe and effective new treatment options. Steins et al. [1] reported that the effective rate of thalidomide monotherapy in AML was 25% and that this treatment could improve transfusion dependence in patients.With improvements in treatment, the complete remission (CR) rate of young patients with acute myeloid leukemia (AML) can be as high as 70% to 80%, and after subsequent consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT), the 5-year overall survival (OS) rate is approximately 40% to 45%. However, the treatment effect is poor in high-risk and el- Objectives. The aim of this study was to investigate the effects and its mechanism of thalidomide and IFN on inhibiting the proliferation of Kasumi-1 cells. Material and Methods. Thalidomide, IFN and a combination of both drugs were used to treat Kasumi-1 cells. The inhibition of cell proliferation and the apoptosis rate were measured. Vascular endothelial growth factor levels and the expression of apoptosis-related proteins were detected by ELISA and Western blotting, respectively. Results. Thalidomide and IFN could both inhibit Kasumi-1 cell proliferation in a dose-dependent manner. When Kasumi-1 cells were treated with thalidomide 350 μg/mL or IFN1400 U/mL for 48 h, the proliferation inhibition rates were (48.8 ± 4.64)% and (50.19 ± 2.59)% and the rates of apoptosis were (14.68 ± 2.61)% and (21.71 ± 0.71)%, respectively; when treated with a combination, the cell proliferation inhibition rate and apoptotic rate were statistically significantly higher than both the control group and the groups treated with a single drug. The ELISA assay revealed that both 350 μg/mL of thalidomide and 1400 U/mL of IFN could reduce the VEGF levels in cell culture supernatants; the two-drug combination group had a further decreased VEGF concentration. Forty-eighthour treatment of thalidomide 350 μg/mL and IFN 1400 U/mL could significantly decrease Bcl-2 expression and increase the expression levels of phosphor-P38, BAX, cytochrome c, and cleaved caspase-3, -8, and -9 as compared to the control group. The combination group exhibited significantly greater extents of reduction in Bcl-2 protein and increases in p-P38, BAX, and cytochrome c, and cleaved caspase-3, -8, and -9 protein expression as compared to the single drug groups. Conclusions. Thalidomide and IFN can synergistically inhibit Kasumi-1 cell proliferation, which is possibly achieved through the mitochondrial and death receptor pathways and through the activation of the P38 signaling pathway to induce apoptosis and by inhibiting Kasumi-1 cell autocrine VEGF secretion (Adv Clin Exp Med 2016, 25, 3, 403-408).