Abstract: Objective To study the effect of ABCE1 gene on proliferation and apoptosis of human large cell lung cancer H460 cells and its mechanism. Methods In vitro cultured H460 cells were divided into group A, group B, group C and group D (normal control group). The cells in groups A, B and C were transfected with ABCE1-siRNA-1, ABCE1-siRNA-2 and ABCE1-siRNA-N, respectively. The siRNA vector of constructed ABCE1 was transfected into H460 cells. The efficiency of transfection was observed under a fluorescence microscope. Expressions of ABCE1 protein, RNase L protein and ABCE1 mRNA were detected by Western blot and RT-PCR, respectively. The proliferation and apoptosis of H460 cells were detected by MTT and flow cytometry, respectively. Results The siRNA vector of constructed ABCE1 was successfully transfected into the H460 cells. The viability of H460 cells in groups A and B and the expression level of ABCE1 were significantly lower whereas the expression level of RNase L protein was significantly higher after transfection than before transfection (P＜0.01). The proliferation rate of H460 cells was significantly lower whereas the apoptosis rate of H460 cells was significantly higher after transfection than before transfection (P＜0.01). Conclusion ABCE1 gene promotes the proliferation and inhibit the apoptosis of H460 cells by blocking the 2-5A/RNase L pathway.