Objective To determine the expression of cathepsin D (CD), cathepsin H (CH) and cathepsin L (CL) in human primary hepatocellular carcinoma (HCC), and to investigate their mechanisms. Methods The protein expression of CD, CH and CL in hepatic specimens consisted of control (n = 17), HCC (n = 37) and paracancerous (n = 28) tissues were detected by immunohistochemistry. The relative values of CD, CH and CL protein expression were examined with absorbent density analysis. Data were analyzed using SPSS11. 5 software. The univariate analysis was used to compare the difference among groups. Results The mean absorbance of CD, CH and CL proteins in HCC tissues (1.21± 0.33, 0. 89 ± 0.22 and 1.16± 0. 25, respectively) were significantly higher in comparison with those in control tissues (0. 19 ± 0. 07, 0. 24 ± 0. 12 and 0. 28 ± 0. 14,respectively) and in paracancerous tissues (0.27±0.13,0. 31± 0.14 and 0. 36±0.15)(all P values =0.0001). Whereas there was no difference between control and paracancerous tissues with respect to CD, CH and CL proteins (P ＞0. 05). Three proteins immunohistochemically appeared as a lot of diffused spots and stripes staining in cytoplasma of HCC tissues,but only a few scatted spots staining was found in control and paracancerous tissues. Conclusion The high expression of CD, CH and CL protein in primary HCC may be important markers for carcinogenesis and malignant progress.