Incidence of drug-drug interactions (DDIs) has been widely reported; however, such reports in pediatric oncology patients still remain scarce. We studied frequency and demographic correlates of moderate and major DDIs at a pediatric oncology ward in Isfahan, Iran. All pediatric oncology patients admitted to the Omid hospital during a 6-month period (2017) who received at least 2 anticancer or non-anticancer drugs concomitantly were included in our study. Potential DDIs between anticancer and non-anticancer drugs during hospitalization was identified using Lexi-Interact on-line software. We detected 194 DDIs with moderate or major severity for our included 115 patients. Mechanistically, most of DDIs (56.4%) were pharmacodynamic. Systematic use of corticosteroids (82.0%), antimetabolites (77.0%), and antiemetic drugs (69.5%) were the most frequent medication classes responsible for detected DDIs. The interaction between aminoglycosides and the third generation cephalosporins was the most common (13.9%) non-anticancer DDI. The only identified interaction between 2 anticancer drugs was doxorubicin with cyclophosphamide. Age, sex, and the number of administered medications were associated with DDIs. Potential moderate or major DDIs occur frequently among pediatric cancer patients. More studies are needed to assess clinical and economic implications of DDIs in pediatric oncology patients.