Objectives To evaluate the association and risk factors of healthcare-associated infection (HAI) and burden of illness among chemotherapy-induced ulcerative mucositis (UM) patients. Methods For this research, US National Inpatient Sample database 2017 was utilized to study UM patients. The association of healthcare-associated infection-related burden of illness among UM patients was assessed on the outcome--length of hospital stays (LOS), total charges, in-hospital mortality, and discharge disposition. Result In 2017, there were 11,350 adult (> 18 years of age) UM patients, among them there were 415 (3.5%) HAI. After adjusting for patient and clinical characteristics, UM patients with HAI were most likely to have higher total charges and longer LOS (1.91; 95% CIs: 1.51-2.41; P < 0.001; 1.84; 95% CIs: 1.53-2.21; P < 0.001) than those without HAI. Further, mortality was not significantly different. UM patients with HAI were less likely to have higher burden of illness who were younger, females, those living in non-metropolitan or micropolitan counties, and those with lower co-morbidity score. Additionally, UM patients with HAI were more likely to discharge to skilled nursing facility (SNF), intermediate care facility (ICF), and another type of facility (ATF), (aOR = 2.58 (1.16-5.76), P = 0.02), than they were to discharge to self-care or home care. Conclusion UM patients with HAI were more likely to have higher burden of illness and more likely to discharged to the SNF, ICF, and ATF rather than to home or self-care. Clinical relevance UM patients when associated with HAI have higher burden of illness; a tailored approach to oral care might prevent HAIs and burden of illness among UM.