Background: The childhood cancer is increasing throughout the world. The incidence of children and adolescent (1-19 years old) mortality by cancer was 4.49 by 2006 (Korea Statistics, 2014). Mothers of children experienced a difficult situation in coping when their children were diagnosed with cancer. Based on Mishel's Uncertainty in Illness Theory, maternal uncertainty and perceived social support are important factors that may have an impact on maternal coping in mothers of children with cancer. Therefore, it was worth to investigate this phenomenon in the context of Korea where no such study was conducted. Objective: To identify the factors affecting maternal coping in mothers of children with cancer. Methods: The study was conducted by using a descriptive design. This study was approved by the Institutional Review Board, Yonsei Health System, Severance Hospital, Seoul, Korea and informed consent forms were obtained from the participants. Fifty-nine mothers completed three questionnaires: 1) Parent's Perception of Uncertainty Scale, 2) Multidimensional Scale of Perceived Social Support, and 3) Coping Health Inventory for Parents. The internal consistency of these instruments was satisfactory, all with alpha coefficients over 0.86. Results: Hierarchical multiple regression analysis revealed that perceived social support and maternal uncertainty together explained 35% of the variance in the maternal coping in mothers of children with cancer (R 2 = 0.353, F = 15.255, p = 0.000). Perceived social support and maternal uncertainty had an impact on maternal coping. Conclusions: The findings provided information that could be used in a further intervention study to increase maternal coping in mothers of children with cancer.