Abstract: Objective: To evaluate the significance of p21, p185, EGFR protein expression and LN, type IV collagen in human osteosarcoma . Methods: p21, p185, EGFR protein expression and LN, type IV collagen were examined in 40 cases human osteosarcoma tissue with immunohistochemical ABC methods. Results: Accumulation of p21 protein was found in 8 out of 38 cases osteosarcomas. The positive rates of p185 andEGFR were respectively 65.8 % and 50.0 %. It was observed that the majority of LN and type IV collagen expression in osteosarcoma was defective. Conclusion: The results of p21, p185 and EGFR high expression in human osteosarcoma suggest that they did have a correlation with osteosarcoma origin and development; The changes of LN and type IV collagen have significant effect on osteosarcoma invade and metastasis.