Background: Childhood cancer is an overwhelming life event that can completely change the lives of the sufferers and their parents. Todays, advances of medical science have shifted the fetal nature of childhood cancer to chronic one exposing children and their family to behavioral and psychosocial problems. The aim of this study was to investigate the effect of filial therapy on children's depressive symptoms and their mother's stress, anxiety, and depression. Materials and Methods: In this randomized controlled trial, 32 mothers with their children who suffered from cancer were recruited (16 in each group). During a 10-week training sessions, filial therapy group underwent child-parent relation therapy (CPRT). Training sessions were held once a week. Control group received no training and only individual counseling sessions were held for them we needed. Both groups were assessed before and after the intervention using depression, anxiety, and stress questionnaire-21 (DASS-21), children depression inventory (CDI), and Wong-Baker faces pain rating scale (WBFPRS). Sample randomization and data analysis were conducted by using SPSS (version 20) and running independent t-test and chi-square test. P value< 0.05 was set as the significant level. Results: Mothers in the filial therapy group experienced significant decrease in their level of depression, anxiety, and stress in the posttest (p < 0.001). In contrast to filial therapy group, mothers in the control group did not show an improvement in their level of depression, anxiety, and stress. Moreover, the results of the current investigative showed that depression of children in the filial therapy group significantly reduced at post-test (p < 0.001). On the other hand, the mean of children's depression in the control group remained steady. Conclusion: The findings of the present study revealed that using filial therapy could reduce the depression of children with cancer and their parent's depression, anxiety, and stress. Accordingly, we suggest filial therapy programs as a routine for addressing psychosocial problems of children with cancer and their families.