Objective: The purpose of this study was to evaluate the early radiotherapy effect using 99Tcm-HL91 SPECT in patients with brain tumors. Methods: Twenty-one patients with brain tumors who were treated by radiotherapy were studied. KPS grade, tumor size on 99Tcm-HL91 SPECT , tumor size on MRI, and ratio of T/N (tumor counts/sec over normal brain tissue counts/sec) were investigated before ,during and after radiotherapy. Results: The average tumor size on 99Tcm-HL91 SPECT and MRI was 11.34(5.88 cm2, 9.46(5.66 cm2, respectively before radiotherapy. The tumor size on 99Tcm-HL91 SPECT was not in accordance with to that on MRI (P＜0.05). KPS grade, tumor size on 99Tcm-HL91 SPECT and ratio of T/N had significance differences before, during and after radiotherapy (P＜0.05), but the tumor size on MRI imaging had no significance differences before, during and after radiotherapy (P＞0.05). The rate of symptom improvement was 80% during radiotherapy and 100% after radiotherapy. The rates of imaging remission based on the brain tumor size on 99Tcm-HL91 SPECT, MRI and T/N were 75%, 15%, and 80%, respectively during radiotherapy. The agreement rates between imaging remission diagnosed by those three methods and symptom improvement were 70%, 40%, and 60% respectively during radiotherapy. The rates of imaging remission based on the brain tumor sizes on 99Tcm-HL91 SPECT, MRI and T/N were 100%, 25%, and 95% respectively after radiotherapy. The agreement rates between imaging remission diagnosed by those three methods and symptoms improvement were 100%, 20%, and 95% respectively after radiotherapy. Conclusion: The tumor size on 99Tcm-HL91 SPECT is a valuable tool for evaluating early radiotherapy effect of brain tumor in process of radiotherapy. T/N is not a feasible method in evaluating radiotherapy effect of brain tumor because it may show elevation unrelated to the curative effect during radiotherapy.