The benefits of play-based occupational therapy for hospitalized children with cancer warrant further exploration. Pediatric cancer disease symptoms, complications from treatment, and multiple and prolonged hospitalizations restrict participation in the daily activities of a child’s life. However, occupational therapy services in pediatric oncology are limited because of the disease nature, treatment complications, hospital environment, and unclear play-based occupational therapy frame. For this purpose, we decided to introduce the process of occupational therapy in such children, using the play-based approach by reviewing the current literature. Considering limitations and problems in hospitalized children with cancer, it seems that controlling symptoms, facilitating independent doing of daily activities, improving the Quality of Life (QoL), and making hospital environment more acceptable are more accessible, using the play-based approach compared with other traditional interventions.