Background and Purpose: Chemotherapy is one of the main options in treating childhood cancers. Fatigue and pain are common symptoms of cancer and one of the major complications experienced during chemotherapy. This study aimed to determine the effect of foot reflexology and simple foot massage on fatigue and pain in children with leukemia. Materials and Methods: This randomized clinical trial was performed on 99 children with leukemia aged 4-14 years, undergoing chemotherapy in the oncology departments of Hazrat Ali Asghar Hospital and Children’s Medical Center, Tehran City, Iran, in 2019. The sampling was sequential, and participants were assigned into three groups by block randomization: Foot reflexology, simple foot massage, and control group. The foot reflexology and simple foot massage were performed for 5 consecutive days. Participants were asked to report the intensity of pain and fatigue over the past 48 hours using the pain visual and child fatigue scales. Statistical analysis was conducted with SPSS software, version 22. Quantitative variables were reported as the Mean±SD. The chi-square test, analysis of variance, and repeated measures tests were used for data analysis. Results: Demographic characteristics in three groups were not significantly different except for gender (P=0.011). There was no significant difference in pain (P=0.67) and fatigue (P=0.45) before the intervention. The Mean±SD pain scores on the third day in foot reflexology, simple foot massage, and control group were 4.4±1.9, 5.2±1.79, and 6.3±1.76, respectively (P<0.001). The Mean±SD pain scores on the fifth day in foot reflexology, simple foot massage, and control group were 2.7±1.4, 3.9±1.83, and 6.7±1.5, respectively (P<0.001). The Mean±SD fatigue scores on the third day in foot reflexology, simple foot massage, and control group were 2.36±0.55, 2.95±0.6, and 3.65±0.32, respectively (P<0.0001). The Mean±SD fatigue scores on the fifth day in foot reflexology, simple foot massage, and control group were 2.14±0.42, 2.67±0.73, and 4.12±0.16, respectively (P<0.0001). Conclusion: Our results showed that foot reflexology and simple foot massage can decrease pain and fatigue in children with leukemia. Performing foot reflexology could be recommended as a complementary intervention to reduce pain and fatigue in children with leukemia.