Objective? To explore the effect of mindfulness-based stress reduction(MBSR) on cancer-related fatigue and mental status of patients with non-small-cell lung cancer(NSCLC) who receive chemotherapy. Methods? By convenience sampling, 67 patients with NSCLC receiving chemotherapy in the First People's Hospital of Lianyungang in Jiangsu Province were selected from June 2017 to December 2018 in this study. According to their admission time, they were divided into the observation group(n=34) and control group (n=33). Conventional nursing care was given for the control group, apart from that, the MBSR exercise was adopted for the observation group, once a week and 8 times in total. Cancer Fatigue Scale (CFS), Self-rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to compare the scores of their cancer fatigue, anxiety and depression between the two groups. Results? Finally, 31 patients in the observation group and 32 patients in the control group completed the study. Before intervention, there was no statistical difference in CFS and each dimensional score in CFS, SAS and SDS scores between the two groups (P＞0.05); after 8 weeks' intervention of MBSR, the CFS score and each dimensional score in CFS, SAS and SDS scores of the observation group were lower than those of the control group, and the differences were statistically significant (P＜0.05). Conclusions? MBSR can effectively improve the NSCLC patients' cancer-related fatigue and reduce the level of anxiety and depression.