Background: Studies have shown the high prevalence of dental caries among children with cancer. Since parents’ awareness affects their children’s oral and dental health, this study was conducted to investigate the awareness and performance of parents of children with cancer regarding oral and dental health. Methods: This descriptive-analytical epidemiological study was conducted on the parents of 3-13-year-old normal (n = 110) and cancer-case (n = 110) children in Ahvaz, Iran, during the fall of 2022. In this study, a researcher-made questionnaire was used. Pearson’s correlation coefficient and regression analysis were utilized to investigate the relationship between awareness and performance. The data were analyzed by SPSS software version 24, and the significance level was P < 0.05. Results: Parents of normal children were more aware of oral and dental hygiene, but it is not statistically significant (P-value = 0.313 < 0.05). The results related to measuring parental performance showed that parents of normal children have a higher performance level than parents of cancer children, which is significant (P-value = 0.000 < 0.05). Conclusions: The awareness and performance of parents of children with cancer regarding their children’s oral and dental health were insufficient. Therefore, parents’ information should be increased in various ways, and children should be referred to a dentist based on a regular plan for preventive and therapeutic goals.