Objective To investigate the expression level of TEC, a no-receptor tyrosine kinase, in hepatocellular carcinoma(HCC) tissues and its correlation with drug resistance. Methods The expressions of TEC mRNA and protein in carcinoma tissues, paracancerous tissues and HepG2 cell line were determined by RT-PCR, Western blot, immunohistochemistrical staining and slot blotting. MTT assay was used to detect the activity of HepG2 cells. A eukaryotic expression vector carrying TEC gene was constructed to obtain high expression level of TEC in HCC, and RNA interference was applied to knock down TEC. Phospho-TEC was also analyzed by CO-IP to determine TEC activation. Results TEC mRNA and protein were both increased significantly in 18 cases of HCC tissues as compared with those in paracancerous tissues(P < 0.001). The high expression of TEC was associated with the increased resistance of 48 cases of HCC tissues to chemotherapeutic drugs; the upregulation of TEC increased the resistance of HepG2 cells to chemotherapeutic drugs. TEC were augmented by the treatment of chemotherapeutics, accompanying with an increase of phospho-ERK. Conclusion TEC is highly expressed in HCC tissues, which is responsible for the drug resistance of HCC and likely related to increased phospho-ERK.