Objective: This study aimed to determine the effectiveness of painting therapy in reducing emotional- behavioral problems (internalized problems: anxious - depressed, withdrawn-depressed, somatic complaints, and externalized problems: aggressive behavior and rule-breaking behavior) of Children with cancer. Method: The research design was quasi-experimental with a pretest-posttest and control group with follow-up. Using targeted sampling, 40children (6 to 12-year-old) with cancer, whose score on the Child Behavior Check List (CBCL) was one standard deviation above average, was selected and randomly divided into two groups of experiment (n = 20) and control (n = 20), but due to the drop in the number of subjects, it decreased to 31 (16 experimental group and 15 control group). The painting program was performed on the experimental group in the form of 8 two-hour sessions. To analyze the data, the mixed variance analysis method was used. Results: The results showed that although the overall score of the internalized and externalized problems was significantly reduced, painting therapy didn’t affect the somatic complaints (of internalized problems) and the rule-breaking behavior (of externalized problems). Conclusions: The results showed that painting therapy can be an effective way to reduce the emotional-behavioral problems of children with cancer. Therefore the findings of this study can have preventive clinical applications.