Abstract: Objective To study the correlation between tumor cell necrosis rate (TCNR) and the possible factors influencing preoperative chemotherapy response for osteosarcoma, with multivariate and univaried analysis, and to investigate the value of those factors in predicting the chemotherapy response. Methods Using clinic opatholigical date of 40 patients with osteosarcoma in our hospital treated with preoperative chemotherapy, the factors such as gender, age, location, duration of symptoms, tumor volume, pre- and post-chemotherapy AKP and LDH, the expression of Pgp before treatment, chemotherapy protocol, the lowest level of blood leucocytes and lymphocyte after chemotherapy, and the type of x-ray appearance, were analyzed and evaluated TCNR after operation. and demanding the influencing pre- and post-chemotherapy changes of the above factors on chemotherapy response with multivariate logistic regression. Results Among 40 patients, 24 with TCNR above 90% ( 60% ).We found that, with univaried factor analysis and multivariate non-conditional logistic regression analysis, the relationship existed between TCNR and tumor volume, post-chemotherapy AKP, the lowest level of post-chemotherapy peripheral blood leucocytes and chemotherapy protocol. Conclusion The major factors influencing preoperative chemotherapy response were tumor volume, post-chemotherapy AKP, the lowest level of post-chemotherapy peripheral blood leucocytes and chemotherapy protocol. Larger tumor volume and higher post-chemotherapy AKP were risk factors and predicted poor chemotherapy response. The lowest level of post-chemotherapy blood leucocytes could reflect the chemotherapy response indirectly; the chemotherapy response of DIA protocol was much better than that of MMIA.