Objective: To explore the application and effect of comprehensive nursing program based on evidence-based concept in patients with HIV-related lymphoma. Methods: 148 patients with HIV-related lymphoma were randomly divided into control group and observation group, with 74 cases in each group (Table 1). The control group was given routine nursing, while the observation group was given comprehensive nursing on the basis of routine nursing. The HIV Self-management Scale, Herth Hope Index and WHO Quality of Life Questionnaire for HIV Brief Version were used to evaluate the score of self-management, hope and quality of life of patients in the two groups before and after intervention. The level of chemotherapy compliance and the incidence of complications were also compared between the two groups. Results: Compared with the control group, the scores of self-management, hope and quality of life in the observation group were significantly higher (P<0.05) , the compliance of chemotherapy and the incidence of complications in the observation group were significantly lower than those in the control group (P <0.05) (Table 2). Conclusion: The comprehensive nursing program based on evidence-based concept can effectively improve the self-management ability, the level of hope and quality of life of the patients with HIV-related lymphoma after chemotherapy, it is worth popularizing in clinic to improve the compliance of patients and reduce the incidence of complications.