Objective To explore the influence of comfort nursing theory on chemotherapy patients with malignant tumor in the perspective of high quality nursing. Methods A total of 120 patients with malignant tumor treated in Beijing Friendship Hospital, Capital Medical University from January 2019 to December 2019 were selected. According to random number table method, they were divided into control group and experimental group, with 60 cases in each group. The control group received routine nursing at the infusion port, on the basis of the control group the experimental group was given nursing intervention in the perspective of high quality nursing comfort nursing theory. After 6 months of follow-up, quality of life, level of hope and psychological status of both groups were evaluated. Results Fifty cases were actually included in the control group and 40 cases were included in the experimental group when invalid questionnaires and patients died of illness were excluded. After 6 months of follow-up, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores in both groups were lower than before intervention (P ＜ 0.05). SAS and SDS scores in experimental group were significantly lower than those in control group (P ＜ 0.05); the scores of positive action and intimate relationship in control group were significantly higher than those before intervention (P ＜ 0.05); the total scores of positive action, intimate relationship and hope in the experimental group were higher than those before intervention (P ＜ 0.05); the scores of positive action, intimate relationship and hope level in experimental group were significantly higher than those in control group (P ＜ 0.05); the quality of life scores in both groups were higher than before intervention (P ＜ 0.05); the scores of physiological function, physiological function, social function and body pain in the experimental group were significantly higher than those in the control group (P ＜ 0.05). Conclusion From the perspective of high quality nursing, the application of comfort nursing theory can reduce the anxiety and depression of patients with malignant tumor in the indwelling infusion port, enhance the level of hope, and improve the quality of life.