Background: Cancer is a leading cause of death for children worldwide.  In high-income countries, more than 80% of children with cancer are cured, but only 20% are cured in many low-income countries. Aim: To evaluate the effect of educational program on the knowledge and performance of caregivers having children with cancer undergoing chemotherapy. Research design:  One group pre-posttest quasi-experimental research design was used in the current study. Sample: A purposive sample of 35 caregivers having children with cancer and undergoing chemotherapy participated in the study. Setting: The current study was conducted at the pediatric unit at Minia Oncology Center. Tools: Tool (I): Structured Interview Sheet:  covered the personal data of the caregivers and the characteristics of the child; Tool (II): Caregivers Knowledge Assessment Sheet and Tool (III): Caregivers Performance Assessment Sheet.  Results: Caregivers having children with cancer who received the educational program had a higher total mean score of knowledge and performance about the care of their children with cancer undergoing chemotherapy than before. Statistically significant differences were detected between the total mean score of caregivers' knowledge and performance before, after, and follow-up of the educational program regarding childhood cancer and chemotherapy. Conclusion: The study concluded that the designed educational program effectively improved caregivers' knowledge and practice regarding the care of their children with cancer undergoing chemotherapy. Recommendation: The study recommended the integration of the designed educational program for caregivers in pediatric oncology units; it would provide a framework for caregivers' role for their children with cancer.