This study aimed to investigate the effect of high-quality nursing intervention on the quality of life (QOL) and psychological state of patients undergoing chemotherapy for the first time. A total of 100 malignant tumor patients admitted to Jiangyin Hospital of Traditional Chinese Medicine to receive chemotherapy for the first time from October 2018 to July 2020 were selected and randomized either to the control group or to the study group (50 cases in each group) via the random number table method. The control group received routine nursing, while the study group received high-quality nursing intervention. There was no striking difference in self-rating anxiety scale (SAS), self-rating depression scale (SDS), Karnofsky score (KPS), Eastern Cooperative Oncology Group (ECOG), and QOL between the two groups before nursing intervention (all P > 0.05 ). After nursing intervention, the SAS, SDS, KPS, ECOG, and QOL in the study group were better than those in the control group (all P < 0.05 ). The adverse reaction scores of the patients in the study group were lower than those in the control group ( P < 0.05 ). High-quality nursing intervention can effectively reduce the psychological pressure of the first chemotherapy for patients with malignant tumor, ameliorate the psychological burden of patients, relieve patients’ anxiety and fear, thus improve the chemotherapy effect, and contribute to improve their QOL.