Objective To explore the effects of behavior changes intervention based on the Multi-Theory Model (MTM) for patients with post-stroke fatigue.Methods A total of 74 inpatients with post-stroke fatigue in neurology department were divided into a control group and an experimental group chronologically, with 37 patients in each group.The control group received routine care, while the experimental group additionally received behavior changes intervention based on the MTM for 3 months.The Fatigue Severity Scale (FSS), the Stroke Self-efficacy Questionnaire (SSEQ) and the Stroke-Specific Quality of Life Scale (SS-QOL) were used to evaluate the two groups before the intervention, 1 month and 3 months after the intervention.Results Totally 36 patients in each group completed the study and follow-up.The time effect, group effect and group by time effect between the two groups in the scores of FSS, SSEQ and SS-QOL were statistically significant (all P＜0.05).One month and 3 months after the intervention, all the indexes in the experimental group were significantly better than those of the control group (all P＜0.05).Conclusion The behavior changes intervention based on the MTM can effectively alleviate patients′ fatigue severity, and improve their self-efficacy and quality of life.