OBJECTIVE: This study discusses the effects of focus training on heart rate variability (HRV) in post-stroke fatigue (PoSF) patients. METHODS: Self-generate physiological coherence system (SPCS) was used for the focus training of PoSF patients for 12 weeks. Then, fatigue severity scale (FSS), Hamilton depression scale (HAMD), HRV and satisfaction scale (SASC-19) before and after the training were assessed. RESULTS: Compared with the control group, FSS score, HAMD score, RMSSD, PNN50% were significantly lower in the research group at the end of the intervention (P < 0.05); SDNN, SDANN, LF, HF, LF/HF intervention satisfaction rate increased significantly in the research group at the end of the intervention (P < 0.05). CONCLUSION: The use of SPCS software during the focus training of PoSF patients reduced the fatigue and depression, meanwhile improved the HRV of the patients. Therefore, these patients were greatly satisfied with the intervention.