Objective: To observe the expression of human leukocytic antigen DR (HLA-DR) in primary hepatocellular carcinoma (HCC) and its up-regulation by interferon (IFN). Methods: The expression of HLA-DR in 46 specimens of human HCC tissues, 4 human HCC cell lines (SMMC-7721, HCC-9204, BEL-7402 and HHCC) and a human hepatocyte cell line QZG was respectively detected by immunohistochemical ABC staining and flow cytometry. The expression of HLA-DR in the 5 cell lines was detected by ELISA before and after the cells were treated with IFN-γ or IFN-α. Results:Eighteen out of 46 HCC tissues (39.1%) expressed HLA-DR, whereas all the normal liver tissues immediately adjacent to HCC tissues were HLA-DR-negative. No obvious HLA-DR-positive staining was found in all the 5 cell lines. The expression of HLA-DR was up-regulated in all the 5 cell lines after IFN-γ or IFN-α treatment. The up-regulation of HI A-DR in QZG cells was less obvious than that in HCC cell lines. The effect of IFN-γ was more significant than that of IFN-α. Conclusion: HCC tissues can express HLA-DR to some extent, but HCC cell lines do not express detectable HLA-DR. IFN can up-regulate HLA-DR expression in HCC cells.