Objective To investigate the application value of apparent diffusion coefficient (ADC) in monitoring the effect of neoadjuvant chemotherapy for osteosarcoma. Methods Twenty-eight osteosarcoma patients underwent MRI before and after the neoadjuvant chemotherapy. ADC values of the lesions were measured before and after treatment. The differences in ADC values before and after treatment in responders and non-responders were analyzed. Results After the neoadjuvant chemotherapy, 21 patients and 7 patients were categorized into the responder group and the non-responder group respectively. The mean pre-treatment ADC values of the responder group and the non-responder group were (1.12 ± 0.16)×10-3 mm2/s and (1.57 ± 0.20)×10-3 mm2/s, respectively. The mean post-treatment ADC values of the responder group and the non-responder group were (2.33 ± 0.18)×10-3 mm2/s and (1.97 ± 0.22)×10-3 mm2/s respectively. The differences in the ADC values between the two groups before and after chemotherapy were statistically different (P < 0.05). The difference in the rates of change of ADC values in the responder and non-responder groups before and after treatment was significant (P < 0.05). Conclusions ADC values enable a good short-term response evaluation for osteosarcoma and the pre-treatment ADC value indicates significant predictive value for responses to the treatment.