Introduction. Leukemia is a broad term that refers to a group of malignant diseases of the bone marrow and lymphatic system. Caregiver burden is one of the issues that are faced by primary caregivers, and this role is played by mothers in most cases. In addition to these problems, mothers experience frustration in performing tasks, isolation and failure due to inadequate education about the disease and inadequate information support. The aim of the present study was to determine the effect of education on the caregiver burden (CB) among mothers of children with leukemia.Material and methods. The present quasi-experimental study was performed on mothers of children with leukemia in the Hematology Ward of Ali ibn Abi Talib Hospital of Zahedan in 2019. Convenience sampling was used to select eligible mothers. At the baseline, the control group was selected according to the inclusion criteria (this method was to prevent the effect of the intervention on the control group). Then, a questionnaire including demographic information, and caregiver burden inventory (CBI) were completed in two stages: pre-test and post-test.To this end, after completing the questionnaire, the first training session was held in the hematology department individually for 30 to 45 minutes with a specific content. Also, after completing three training sessions, phone follow-up was performed weekly for 4 weeks to ensure that the intervention was implemented. The questionnaires were redistributed and recompleted by intervention and control groups again four weeks after the intervention.Results. The mean pre-intervention CB score in the intervention and control groups was 19.97 ± 5.25 and 18.97 ± 10.03, respectively. The mean post-intervention CB score was also 17.17 ± 4.78 and 19.18 ± 9.93, respectively. Intervention significantly reduced CB score in the intervention group (p < 0.001).Conclusions. The findings showed that training was effective in reducing the CB score among mothers of children with leukemia. Therefore, it is recommended to use training as a non-pharmacological and appropriate method in reducing CB among mothers of children with leukemia.