Providing oral care hygiene for children at intensive care unit and protecting oral mucosa are important in the promotion of healthy nutrition, comfort, and improving patients' quality of life, as well as preventing mucositis. Aim: to evaluate the role of chlorhexidine in preventing mucositis among ventilated children. Subjects and Method: design: Quasi-experimental research design was used in this study Sample: The study included 60 children (>6 years age) admitted to PICU and needed mechanical ventilation. They were divided into two groups: group one (30 children) who had oral care intervention (tooth brushing and 0.12% Chlorhexidine gluconate solutions) and group two (30 children) who received routine hospital care. Setting: This study was conducted in pediatric intensive care Units at Assiut University Children Hospital. Data collection tools included: socio-demographic and clinical data structured interview questionnaire, oral mucositis assessment scale, and oral cavity assessment tool. Results: The majority of children (93.3%) in group one (study) had a normal oral condition after intervention, compared to 10.0% had normal oral condition in group two (control) after intervention with a highly statistically significant difference between the study and control groups. Conclusion: In mechanically ventilated children, oral care interventions such as tooth brushing and CHX gluconate dramatically reduced the prevalence of mucositis. Recommendations: Chlorhexidine gluconate 0.12% is recommended as a mouth rinse for patients who are intubated orally.