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The β-galactoside α2-6-sialyltransferase 1 (ST6Gal-Ⅰ) is the principal sialyltransferase responsible for the addition of α2-6-sialic acid to the termini N-glycans on cell surface.Although ST6Gal-Ⅰ in cancer cell resistance to chemotherapeutics agents has been previously reported,the role of ST6Gal-Ⅰ in clinical drug resistance of hepatocellular carcinoma (HCC) is not fully understood.In this study,we found that knockdown of ST6Gal-Ⅰ increased the sensitivity of hepatocarcinoma MHCC97-H cells to docetaxel treatment by instigating the process of apoptosis.Silencing ST6Gal-Ⅰ expression decreased the survival rate of MHCC97-H cells after docetaxel treatment.Importantly,ST6Gal-Ⅰ silencing resulted in an increasing of phospho-p38,Bax,Bad,cytochrome c and the cleaved caspase-9,3 and PARP,while a decreasing of the anti-apoptotic protein Bcl-2.In addition,we found that p38 MAPK and caspase-3 inhibitors can reduce the enhanced apoptosis levels of MHCC97-H cells resulted by either ST6Gal-Ⅰ silencing or docetaxe1 treatment.Conversely,exogenous expression of ST6Gal-Ⅰ in hepatocarcinoma Huh7 cells inhibited apoptotic cell death and prevented docetaxel-induced apoptosis by inhibiting p38 MAPK mediated mitochondrial-dependent pathway.Taken together,these results indicate that ST6Gal-Ⅰ might play a positive role in mediating the survival of human hepatocarcinoma cells and could be a potential target for gene and antitumor drugs therapy.