Introduction and significance of the study: Chemotherapy is a long-term treatment and leads to many acute side effects. Fatigue is recognized as one of the most common and distressing symptoms experienced by pediatrics with cancer. The prevalence of fatigue during cancer treatment ranges from 25 to 99%. Some chemotherapy drugs could cause painful side effects, such as aching in the muscles and joints, headaches, and stomach pains. Pain may be felt as a burning, numbness, tingling, or shooting pains in the hands and feet. This type of pain can last long after treatment ends. Chemotherapy not only negatively affect a child’s sense of well-being, but also their daily functioning, activities, and relationships with family and friends. Massage is a stand-alone nursing intervention that could be used to help patients who are in pain. Massage is simple to do, inexpensive, and requires no special equipment. It might be incorporated into routine nursing tasks. Therefore, foot massage is one of the most popular types of massage because it has the potential to help relieve pain. Massage therapy improves blood circulation. This allows the body to feel more relaxed and energized while reducing muscle tension and pain. Aim: This study aimed to determine the effect of foot massage on physiological indicators, fatigue, and pain among children undergoing chemotherapy. Subjects and Methods: Research design: A quasi-experimental research design was used in this study. Setting: The study was conducted at the Oncology Institution in Sohag City and Pediatric Oncology Department, at Sohag University Hospital. Subjects: A purposive sampling technique was used to choose a sample of 100 children undergoing chemotherapy who were assigned into two groups, with 50 children undergoing chemotherapy in each group (the intervention and control groups). Data collection Tools: Three tools were used: (I) Structured Interview Questionnaire composed of two parts (1) demographic data which consists of five items related to age, gender, educational level, residence, and duration of the disease. (2) It included the physiological indicators of the children; it consisted of 3 items about heart rate, systolic blood pressure, and diastolic blood pressure. (II): Fatigue assessment scale. (III): OUCHER pain measurement tool. Results: The current study revealed that the mean age of the studied children was (7.08 ± 2.34 and 7.89 ± 2.86) years in the control group respectively. The means of systolic blood pressure (SBP) and diastolic blood pressure (DBP) after intervention in the intervention group were 89.35 ± 16.67 mmHg and 57.87 ± 12.8 mm Hg, respectively. However, the means of SBP and DBP after intervention in the control group were 97.49 ± 14.27 mm Hg and 58.63 ± 10.32 mmHg, the mean of SBP and DBP after intervention between the two groups were (p < 0.0001 and p = 0.002) respectively. The mean heart rate (HR) after intervention in the intervention and control group was (91.46 ± 15.2 and 96.7 ± 10.4) respectively. There was a significant difference in the mean HR after intervention between the two groups with (p = 0.003). The mean pain after intervention in the intervention and control group was 35.14 ± 14.62 and 43.52 ± 16.45. The mean pain intensity was significantly lower in the intervention group than in the control group with (p < 0.0001*). The majority of studied children undergoing chemotherapy in the intervention group and the control group (80% and 81%) respectively had a moderate level of pain pre-intervention. But post intervention 67% of the studied children had a mild level of pain in the intervention compared to 19% in the control group. Conclusion: Based on the findings and hypotheses of this study, it was concluded that foot massage was effective in improving physiological indicators and reducing fatigue levels and pain among children undergoing chemotherapy in the intervention group when compared to the control group after the intervention. Recommendations: The study recommended that foot reflexology can be used as a complementary treatment along with conventional therapies among children undergoing chemotherapy as a simple and applicable strategy to improve physiological indicators, reduce fatigue levels and pain.