〔Abstract〕 Objective To investigate the influence and molecular mechanism of hypoxia-inducing factor-1α(HIF-1α) gene silencing combined with methyl selenenic acid(MSA) on cervical cancer cell proliferation, apoptosis and cell migration. Methods HeLa cells were transfected with HIF-1 interference RNA and negative control RNA. After transfection for 48 h, cells were stimulated with MSA for 24 h, and cell proliferation was determined by CCK-8 assay and colony formation. Apoptosis was determined by flow cytometry combined with Annexin V-FITC/PI. The expression levels of HIF-1α, Bcl-2, and E-cadherin were detected by Western blot assay. Cell migration ability was determined by Transwell assay. RNA-seq analysis was used to investigate the differentially expressed genes and differential signaling pathways. Results Compared with the control group, interfering with HIF-1α combined with MSA significantly inhibited cell proliferation(P<0.01). Flow cytometry results showed that the combined drug group significantly induced apoptosis. Transwell results showed that interfering with HIF-1α combined with MSA inhibited He La cell migration. Compared with the control group,interfering with HIF-1α combined with MSA downregulated the expression of Bcl-2 and up-regulated the expression of E-cadherin. RNA-sequencing combined with signal pathway enrichment results showed that the expression of apoptotic signal pathway and downstream genes was inhibited. Conclusion HIF-1α gene silencing combined with MSA can synergically inhibit the proliferation and induce apoptosis of cervical cancer cells,and its regulatory mechanism may be related to the expression of Bcl-2family proteins and the inhibition of p53 signaling pathway.