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Background: Recurrent respiratory papillomatosis (RRP) is caused by HPV types 6 and 11 and has a substantial papilloma growth in the airway and is recurrent. The activity of HPV neoplasms is related to the cell cycle, a complex series of processes that cause cells to grow and replicate. The p53 and Ki67 proteins, as one of the tumor gene controllers, have the function of controlling the cell cycle and assisting the apoptotic process of damage to DNA. Objective: This study aims to analyze the relationship between RRP aggressiveness and p53 and Ki67 protein expression as one of the predictive factors for aggressive disease progression. Methods: This study was an observational analytic study with a crosssectional form. The p53 and Ki67 protein examination results were obtained from immunohistochemical examination by staining monoclonal antibody rabbit Anti-Human p53 and Ki67 clone 318-6-11. Data analysis used binary logistic regression to determine the relationship between the independent and dependent variables with a significant p <0.05. Results: From 19 samples, the distribution of the sex distribution of male patients (42.10%), while for women of eleven patients (57.90%). The type of RRP that was served the most by the participants was RPP for 13 children (68.40%). Positive p53 protein expression was found in 8 (42.10%) patients, while 11 (57.90%) patients had negative p53 protein expression. Moreover, on positive Ki67 protein expression, there were 5 (26.30%) patients and 14 (73.70%) patients with negative Ki67 protein expression. Discussion: High p53 protein expression indicates that the cell cycle is not controlled, so it is regulated by the p53 protein to control the cycle through the process of apoptosis or capture. The uncontrolled cell cycle causes tumors to grow very fast. Meanwhile, high Ki67 protein expression indicates an uncontrolled cell cycle because most of them are not resting. Conclusion: There is no relationship between the aggressiveness of recurrent tract papillomas with p53 and Ki67 protein expression. [ABSTRACT FROM AUTHOR]