Objective To explore the effect of exercise intervention on cancer-related fatigue and quality of life in children with acute leukemia during chemotherapy. Methods A total of 60 children with acute leukemia were divided into two groups according to either of the two periods they were hospitalized. The control group received routine nursing, while the intervention group was additionally subjected to an exercise intervention program(including pre-exercise assessment, exercise in pursuant to patients′ exercise load, monitoring during exercise) during chemotherapy. The Multidimensional Fatigue Scale (MFS) and Pediatric Quality of Life Inventory 4.0 (PedsQL4.0) were used to evaluate the effect. Results Twelves weeks into the intervention, the scores of fatigue and quality of life in the intervention group were significantly higher than those in the control group (P<0.05 for both). Conclusion Exercise intervention for children with acute leukemia during chemotherapy can effectively improve cancer-related fatigue and quality of life of children.