Chemotherapy treatment often causes side-effects like fatigue in cancer patients. The treatment and diagnosis of cancer can cause depression, which could lead to inflammatory changes in the body, and it is involved in fatigue pathophysiology. This study aims to determine the relationship between depression and fatigue. A cross-sectional design was used, and a consecutive sampling method with a sample of 30 children with cancer aged 8–12 years. This study used two instruments, which are the Fatigue Onkologi Anak-Allen (FOA-A) questionnaire and Centre for Epidemiological Studies Depression Scale for Children (CES-DC). The results showed a significant relationship between depression and fatigue (p = 0.003) and between types of cancer and fatigue (p = 0.018). These results indicated that children with cancer and depressive symptoms felt higher fatigue. Nurses need to assess the fatigue and depression felt by children so they can perform appropriate nursing interventions to reduce their fatigue.