Objective To explore the effect of antidepressant intervention on mood state of at or around the time of radiation therapy. Methods 62 hospitalized patients with cancer receiving radiotherapy were divided into two groups by the order of the time when they accept the radiotherapy which called intervention group ( antidepressant fluoxetine group) and control group. And the two groups patients filled out Hamilton Anxiety Scale( HAMA )and Hamilton Depression Scale (HAMD) at or around the time of radiation therapy to investigate the effects of fluoxetine on anxiety and depression. Results The scores of HAMA and HAMD showed that there was no differences between the intervention group and the control group before the radiotherapy. There was significant difference during the radiotherapy ( 6.41 ± 2.30 ) vs ( 9.29 ± 5.62 ); ( 8.80 ± 3. 048 ) vs ( 12.22 ± 8.32 ) and two weeks after the end of the radiotherapy ( 4.90 ± 1.71 ) vs ( 12.32 ± 7.24 ); ( 6.83 ± 2.47 ) vs ( 16.09 ± 8.61 ) between antidepressant fluoxetine group and control group(P ＜ 0.05 ). Conclusion More attention should be paid to mental health and antidepressant can alleviate anxiety and depression of the cancer patients'at or around the time of radiotherapy.