Objective: Chemotherapy and radiotherapy, used to treat childhood hematological malignancies (HM), can negatively impact oral tissues and organs. This study aimed to evaluate oral health-related quality of life in children with HM. Material and Methods: A total of 99 children, including 49 undergoing HM (41 for acute lymphocytic leukemia, 8 for acute myelocytic leukemia,) and 50 healthy volunteers, were included in this cross-sectional study. The mean age of the entire study group was 78.63 ± 34.41 months. The mean age of the HM and control groups was 87.12 ± 35.04 and 70.95 ± 34.85 months, respectively. The Simplified Oral Hygiene Index (SOHI), Decayed, Missing, and Filled Teeth (DMFT/dmft) index, and Turkish version of the Early Childhood Oral Health Impact Scale (ECOHIS-T) were administered to all children. The data were analyzed using SPSS software (version 22.0). Results: The age and gender distributions of the two groups were similar. The SOHI was significantly higher in the HM group, whereas the DMFT/dmft score was similar between the groups. No significant difference in the total ECOHIS-T score was observed between the two groups, but there was a group difference in the responses to questions on pain and psychological processes. Conclusions: Oral health and self-care were negatively affected by childhood HM and the treatment thereof. Close clinical dental follow-up of such patients is required.