Objective To explore the effect of applying risk assessment combined with plan-do-check-action (PDCA) cycle method to improve the management of healthcare-associated infection (HAI) and its impact on relevant HAI indexes. Methods According to risk assessment results and analysis in 2017, PDCA cycle method was used to implement the common and individual intervention measures for each clinical department in a hospital, risk assessment was conducted again in 2019, two risk assessment results were compared. Results The risk assessment in 2019 showed that most departments were at a medium risk level, the high-risk departments were obstetrics, neurosurgery, and neonatology. In 2019, the number of extremely high-risk departments dropped by one and the number of medium-risk departments increased by one; department of neurosurgery dropped from extremely high-risk to high-risk, obstetrics upgraded to high risk department, department of critical care medicine and neurosurgery intensive care unit (ICU) were still extremely high risk departments. Compared with the monitoring data in 2017, the compliance rate and accuracy rate of hand hygiene in 2019 improved significantly, incidence of HAI and multidrug-resistant organism (MDRO) HAI reduced significantly, differences were all statistically significant (P < 0.05). Conclusion Through the risk assessment combined with PDCA cycle method, focusing on key departments, key links and factors, as well as continuous and effective promotion of HAI management, incidence of HAI can be reduced.