Objective To alleviate fatigue in patients with depression. Methods A total of 94 inpatients with depression were chronologically divided into a control group and an intervention group, with 47 cases in each group. The control group were given routine psychiatric treatment and nursing care, while the intervention group additionally received interventions on fatigue based on the information-motivation-behavioral skills model for 8 times. Before and after the intervention, the Multidimensional Fatigue Inventory (MFI-20), Montgomery and Asberg Depression Rating Scale (MADRS) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate fatigue severity, depression severity and sleep quality of the two groups. Results All participants completed the study. The MFI-20，MADRS and PSQI scores after the intervention had significant differences between the two groups (P<0.01 for all). Conclusion The information-motivation-behavioral skills model based interventions can significantly alleviate fatigue and depression severity in patients with depression，and enhance sleep quality.