This research was carried out to study the effectiveness of acceptance and commitment therapy on depression in nurses. The method in this research was quasi-experimental with pretest and posttest design with control group. The statistical population in this research included all nurses in Shiraz County Dena Hospital during 2018. The sample included 30 participants who were selected through purposive sampling and they were randomly divided into two groups of experiment (15 members) and control (15 members). The data collection instrument n this research was Beck Depression Inventory-II (BDI-II). In order to analyze the data, analysis of covariance (ANCOVA) was used by SPSS. The results indicated that acceptance and commitment therapy had led to a decrease in the depression of the nurses, comparing to the control group. (p<0.01) Hence, acceptance and commitment therapy is an effective method in decreasing depression.