Background: The purpose of this study was to investigate the effect of brain education-based exercise and KPEM manual therapy integrated program on the sleep and quality of life of cancer patients. Design: Seventy subjects who were diagnosed with cancer and were undergoing treatment volunteered to participate in this study. All subjects used a nonequivalent control group pretest-posttest design for either the experimental group or the control group. In the final analysis, there were 25 subjects in the experimental group and 18 subjects in the control group. Methods: For 12 weeks, the experimental group performed brain education-based exercise (20 minutes) and KPEM manual therapy (50 minutes), and the control group performed basic physical therapy and autonomous exercise. For evaluation, the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) and the quality of life index were measured after intervention using the European Organization for Research and Treatment of Cancer (EORTC-3.0Ver). Effect between groups, time effect over time, and group*time interaction were analyzed through a pre-test before and after the 12-week intervention period, and repeated measure ANOVA after 12 weeks of the integrated program intervention. All statistical significance levels were set at α=.05. Results: The PSQI in the time effect (p=.001) and the group*time interaction (p<.001) were statistically significant. In terms of EORTC, QL2 and PF2 were significant in time effect (p=.024; p=.021) and group*time interaction (p=.007; p=.021), whereas in RF2, significance was only found in group*time interaction (p=.028). In symptom indicators, time effect was the only significant factor in FA, SL, AP, and CO, respectively (p=.002; p=.028; p=.041; p =.005) and in DY, there were significant differences in the time effect (p=.016) and group*time interaction (p=.002). Conclusion: The brain education-based exercise and KPEM manual therapy integrated program effectively improves the sleep and quality of life of cancer patients. It is considered that this exercise and therapy can be actively used as a psychological, emotional, and physically complementary physical therapy intervention to improve the quality of life of cancer patients.