Background: The parents of children with cancer suffer from different physical and psychological health problems due to the burden of caregiving to their ill children. The Caregiver Burden Inventory (CBI) is among the most commonly used instruments for caregiver burden assessment. There is no data about its psychometric properties among the parents of children with cancer in Iran. Objectives: This study aimed to evaluate the psychometric properties of the caregiver burden inventory in parents of Iranian children suffering from cancer. Methods: This methodological study was conducted from April to September 2018 in the southwest of Iran. CBI was translated into Persian through the forward–backward method, and its face and content validity were assessed through both qualitative and quantitative methods. Then, its construct validity was assessed using exploratory and confirmatory factor analyses, and its reliability was assessed using the internal consistency and the test-retest stability assessment methods. The data for exploratory and confirmatory factor analyses were obtained from two separate samples of 125 parents. Results: From the 24 items, two items were deleted during content validity assessment due to their incompatibility with the Iranian culture. The impact scores, content validity ratios, and content validity indices of the remaining 22 CBI items were respectively more than 1.5, 0.46–1, and 0.80–1, and the scale-level content validity index was 0.8. Exploratory factor analysis revealed a five-factor structure for the Persian CBI which explained 64.24% of the total variance. Confirmatory factor analysis confirmed the five-factor structure. The Cronbach's alpha and the test-retest intraclass correlation coefficient of the Persian CBI were 0.907 and 0.90, respectively. Conclusion: The Persian CBI has acceptable psychometric properties and can be used to assess caregiver burden among the parents of children with cancer in Iran.