Objective To investigate the expression of heparanase in non-melanoma skin cancer including cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC) and the relationship among heparanase expression and pathologic grading and lymph nodes metastasis of CSCC. Methods The expressions of heparanase were detected by RT-PCR assay and immunohistochemical staining in 38 cases of CSCC, 33 BCC and 19 normal human skin tissues. Then the relationship between heparanase expression and CSCC clinical pathological features was explored. Results The positive rate ( 68.4%, 60. 5% ) of heparanase mRNA and heparanase in CSCC (24. 2%, 18. 2% ) was significantly higher than those of BCC and normal skin tissue ( 10. 5% ,5.3% ) ( P <0. 01 ) . Heparanase expression rate in CSCC with lymph nodes metastasis (92. 3% ,84.6% ) and Ⅲ～Ⅳ(Broders) (92. 3% ,84. 6% ) was higher than those in tumor without lymph nodes metastasis (56. 0% ,48.0% ) and Ⅰ～Ⅱ (Broders) (56. 0% ,48. 0% ) ( P <0. 05). Conclusions Heparanase was over-expressed in CSCC compared with BCC and normal skin tissues. Expression of heparanase was correlated to pathologic grade and lymph nodes metastasis of CSCC.