Interferon regulatory factor (IRF)-1 is one important transcriptional factor and exerts critical roles in anti-virus and anti-tumor. Lymphatic enhancing factor (LEF)-1 is widely expressed in various tissues, and is significantly up-regulated in tumor tissues/cells, thus is believed to be correlated with tumor occurrence and progression. However, the role of IRF-1 on tumor progression via regulating LEF-1 has not been reported. In vitro cultured colon cancer cell line HCT116 was randomly divided into five groups, which were transfected with pcDNA3.1-IRF-1 plasmid, empty plasmid, siRNA-IRF-1, scramble siRNA control, or empty control respectively. Real-time PCR was used to test mRNA level of IRF-1 and LEF1, while LEF1 protein expression was quantified by Western blotting. MTT assay was used to detect proliferation of tumor cells, while Transwell chamber assay was deployed to analyze cell invasion. The activity of Caspase 3 was further measured by test kit. The over-expression of IRF-1 significantly inhibited mRNA and protein expression of LEF1, inhibited tumor cell proliferation, elevated Caspase 3 activity and suppressed tumor invasion (P<0.05 compared to control group). siRNA interfered with IRF-1 expression and significantly facilitated LEF1 expression, thus potentiating tumor cell proliferation, depressing Caspase 3 activity, and increasing tumor invasion (P<0.05 compared to control group). IRF-1 can regulate LEF1 expression, as the up-regulation of IRF-1 can inhibit LEF1 expression, further mediating tumor occurrence and progression.