Objective: To explore the effect of nursing intervention based on mindfulness decompression therapy on cancer-related fatigue (CRF) and mental health of elderly widowed patients with lung cancer undergoing chemotherapy. Methods: From June 2017 to March 2019, 114 elderly widowed patients with lung cancer undergoing chemotherapy were randomly divided into a control group and an intervention group, 57 cases in each group. The control group was given routine medical cancer chemotherapy nursing, and the intervention group was given mindful decompression therapy-based nursing intervention on the basis of the control group. The Revised Piper Fatigue Scale (RPFS), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and European core questionnaire on quality of life (EORTC) were used in the intervention group. QLQ-C30 and other tools were used to compare the effect of nursing intervention between the two groups. Results: After 8 weeks of intervention, the four dimensions and total scores of RPFS scale, HAMD score and HAMA score in intervention group were lower than those before intervention, and also significantly lower than those in control group (P<0.05). After intervention, the five dimensions and total scores of QLQ-C30 scale in intervention group were higher than those before intervention (P<0.05), and there were significant differences between intervention group and control group (P<0.05). There were no statistical differences in RPFS score, HAMD score, HAMA score and QLQ-C30 score before and after intervention in control group. Learning significance (P>0.05). Conclusion: Mindfulness decompression therapy can reduce cancer-related fatigue in elderly widowed patients with lung cancer undergoing chemotherapy, improve their mental health and quality of life.