Objective:To investigate the role of tazarotene induced gene-2(TIG2) in the pathogenesis of skin squamous cell carcinoma(SCC). Methods:TIG2 protein and mRNA in normal skin tissues,uninvolved skin and SCC lesions were detected by immunohistochemistry and hybridization in situ. Results:TIG2 protein and mRNA were expressed in all layers of normal and uninvolved epidermis. In addition, TIG2 expression could be observed in the corneum,granular layers and the upper or middle layers of stratum spinosum of the marginal part of SCC lesions. Furthermore,TIG2 positive expression could only be observed slightly around the keratin pearls of SCC Ⅰ~Ⅱ stages,and no expression in SCC Ⅲ~Ⅳ stages. TIG2 expression is less in aggressive SCC compared with that in the normal skin and uninvolved tissues from SCC(P < 0.01); and TIG2 expression is absent in the basal layer of marginal epidermis of SCC compared with that in normal skin and uninvolved tissues from SCC patients(P < 0.01);moreover,TIG2 expression is also less in SCC Ⅲ~Ⅳ than in the marginal tissues of SCC(P < 0.01). Conclusion:TIG2 may play an important role in the pathogenesis of SCC.