Abstract: Objective To investigate the effects of the human S100A6 on β-catenin in human osteosarcoma cell lines MG63 and U2OS . Methods Cell lines MG63 and U2OS were infected by recombinant adenoviruses carrying the human S100A6 and its siRNA gene, AdS100A6 and AdSiS100A6, respectively, to up-regulate and down-regulate the expression of S100A6. Then RT-PCR，Western blot and immunocytochemistry were used to detect mRNA and protein (level and/or distribution ) of β-catenin. Results In both cell lines MG63 and U2O S, with up-re gulation of S100A6, the expression of β-catenin mRNA and protein increased（P＜0.05）and β-catenin protein increase was more obvious in nuclear than in cytoplasma; while down-regulating S100A6, both the mRNA and protein level of β-catenin decreased（P＜0.05）; β-catenin protein decrease was more obvious in nuclear than in cytoplasma, too. Conclusion. Increaseing Wnt/β-catenin signaling activity may be a mechanism that S100A6 involves in tumor development.