Abstract: Objective It is reported that FHL2 is able to interact and then promote the transcriptional activity of β-catenin. The aim of this study is to evaluate the effect of fhl2 siRNA on the transactivities of β-catenin and its downstream gene, survivin. Methods (1) survivin fragment amplified by PCR was inserted into PGL-basic vector to establish recombinant plasmid named as pluc340 which contained luciferase promoter at the downstream. (2) pTOPFLASH, pFOPFLASH, siRNA and pluc340 were transfected into gastrointestinal cells to detect their transactivities by dual-luciferase assay. (3) mRNA expressions were detected by RT-PCR. Results survivin promoter was established successfully. The transactivity of β-catenin was significantly higher than that in the normal cells. The transcriptional activities of β-catenin and survivin were suppressed by fhl2 siRNA. Conclusion The results indicated that FHL2 inhibition was capable of suppressing the transcriptional activity of β-catenin and thus interfering the process of Wnt signaling pathway. Therefore, fhl2 might be a promising target for innovative treatment of colon cancer.