Chemotherapy, the main treatment method of AL, can produce varying degrees of toxic and side effects on patients while killing tumor cells, resulting in decreased immune function of patients. We aim to explore the application effect of high-quality nursing intervention based on humanistic care combined with the project teaching method on patients with acute leukemia (AL) undergoing chemotherapy and its effect on their psychological state and satisfaction. 114 AL patients undergoing chemotherapy in the Department of Hematology of our hospital from July 2018 to July 2020 were chosen as the research objects and equally randomized into the experimental group (EG) and control group (CG). CG received routine nursing during chemotherapy, while EG received high-quality nursing intervention based on humanistic care combined with the project teaching method. Hospital Anxiety and Depression Scale (HAD) was adopted to evaluate the psychological state of patients in both groups after intervention, and the self-made nursing satisfaction questionnaire in our hospital was applied to evaluate the clinical nursing satisfaction. The HAD-A and HAD-D scores in the CG ( P < 0.001 ) were significantly higher than the HAD-A and HAD-D scores in the EG after intervention. The scores of various coping styles in the EG after intervention were better than those in the CG ( P < 0.05 ). Compared with the CG, the total nursing satisfaction after intervention was remarkably higher in the EG ( P < 0.001 ), while the total incidence of adverse reactions during intervention was notably lower ( P < 0.05 ). High-quality nursing intervention based on humanistic care combined with the project teaching method for AL patients undergoing chemotherapy can effectively relieve negative emotions, improve clinical nursing satisfaction, and reduce adverse reactions during chemotherapy.