Background: Participation in daily life activities is an essential aspect of health, which can facilitate a child’s development. Children with cancer are at risk of functional limitations and participation restrictions. The present study aims to investigate participation of children with cancer in daily life activities compared to healthy peers. Methods: This was a comparative cross-sectional study. In the first phase, we assessed the test-retest reliability of the Iranian Children Participation Assessment Scale in 30 children (6-12 years of age) diagnosed with cancer and their parents (child and parent versions). The second phase of the study included a comparison of daily life activities as measured by the Iranian Children Participation Assessment Scale between the children with cancer (diagnosed at least 4 months prior and currently receiving active treatment) and their age- and gender-matched healthy peers. Results: The child version had excellent reliability according to Cronbach’s alpha in diversity of activities (0.97), intensity of participation (0.95), with whom they participated (0.95), and enjoyment of daily activities (0.94). The parent version had excellent reliability (Cronbach’s alpha) as follows: 0.99 for diversity, 0.97 for intensity, 0.97 for with whom, 0.98 for enjoyment, and 0.98 for parents’ satisfaction. The coefficients of agreement were 0.77 (total scores of diversity), 0.63 (intensity), 0.60 (with whom), and 0.91 (enjoyment). The child version indicated that children with cancer had significantly lower scores in daily life activities items of diversity (P=0.000), intensity (P=0.000), with whom (P=0.000), and enjoyment (P=0.000) compared to healthy children. Based on the total scores in the parent version, children with cancer showed significantly lower scores in diversity (P=0.001), intensity (P=0.000), with whom (P=0.001), enjoyment (P=0.002), and satisfaction (P=0.000) compared to the healthy group. Conclusion: The findings of the present study show that cancer diagnosis and treatment can restrict children’s participation in daily life activities. Early planning and intervention to facilitate participation in these activities can minimize negative consequences and may mitigate or prevent adverse long-term functional effects of childhood cancer.