Leukemia in children is a life-threatening disease and chemotherapy is a complex treatment with severe side effects and complications. Furthermore, the treatment results are unpredictable. This leads to uncertainty in illness resulting in psychological distress. This descriptive cross sectional study aims to examine the predicting factors of uncertainty in illness among children with leukemia undergoing chemotherapy. Ninety-six children with leukemia undergoing chemotherapy in four tertiary hospitals in Bangkok participated in this study. The research instruments included the Children’s Uncertainty in Illness Scale, the Symptom Pattern Scale of Children with Cancer, the Information Support from Health Care Provider Scale, the Information Support from Parent Scale, the Information Support from Peer Scale, the Illness Knowledge Scale, and the Parent Perception of Uncertainty Scale. The results of stepwise multiple regression analysis revealed that symptom pattern, information support from health care providers, illness-related knowledge, and parental uncertainty accounted for 34.8% of variance in uncertainty in illness among the participants. This study provides more understanding for predicting factors of child uncertainty. The results of this study can be used for developing a nursing intervention to reduce uncertainty in illness among children with leukemia undergoing chemotherapy if nurses help them to better understand symptoms as having a pattern, provide information support and illness related knowledge, and decrease parental uncertainty.