Background: One of the non-pharmacological methods for relieving pain in children is to deploy cognitive-behavioral interventions such as distraction therapy. Objectives: The aim of the present study was to examine the impact of distraction on physiological indices and the severity of pain caused by intra-spinal injection of chemotherapy drugs in children with cancer. Methods: This was a clinical trial with a pretest-posttest design. The subjects included 89 cancerous children aged 6-12 years who had been admitted to the Hematology Ward of Ali Ibn Abitalib Hospital, Zahedan, Iran. The patients were divided into the intervention (n = 45) and control (n = 44) groups. In order to distract the children, they were asked to choose one out of three animated series based on their interest. They received the injection while watching the cartoon. Then, the severity of pain caused by intra-spinal injection of the chemotherapy medication, heart rate, and arterial oxygen saturation (SaO2) were evaluated. Results: Arterial oxygen saturation of the intervention group increased from 95.42 ± 4.53 before distraction to 98.04 ± 2.20 after distraction (P < 0.001). The mean heart rate in the intervention group decreased from 108.64 ± 13.36 before distraction to 104.00 ± 12.25 after distraction, suggesting a significant difference between the two groups (P = 0.04). The mean changes in the heart rate were significantly different between the two groups (P < 0.001). Moreover, the mean pain intensity after distraction was significantly lower in the intervention group (35.11 ± 14.71) than in the control group (42.5 ± 16.44) (P = 0.02). Conclusions: Based on the results, distraction therapy can be effective in mitigating the severity of pain caused by intra-spinal injection and improving hemodynamic indices (heart rate and SaO2).