Background: Healthcare-associated infections (HAIs) are a global health issue and a key driver of the increasing occurrence of antimicrobial resistance (AMR). The overall aim of this PhD thesis was to estimate HAI prevalence, analyse the risk factors associated with HAIs, and calculate the additional direct economic burden attributable to HAIs and AMR in a selected Chinese general hospital. Methods: Two systematic reviews and meta-analyses were conducted to identify potential risk factors associated with HAIs and estimate the direct economic burden attributable to HAIs among Chinese general hospitals at a national level from the published literature. Additionally, a cross-sectional study was conducted in a selected Chinese general hospital. Data were extracted from relevant sources spanning 2017 to 2020. Descriptive analysis was used to calculate the annual HAIs prevalence. A chi-square test and binary logistic regression models were applied to investigate the potential risk factors associated with HAIs. A propensity score matching method was employed to select two balanced groups to estimate the additional direct economic burden attributable to HAIs and AMR by assessing the differences in health expenditure and length of hospitalisation. Results: The first systematic review revealed that HAIs were significantly associated with certain socio-demographic characteristics, including age older than 60 years (OR: 1.74, 95%CI [1.38-2.19]) and male sex (1.33[1.20-1.47]). Other factors included invasive procedures (3.54[1.50-8.34]) and health conditions such as chronic diseases (1.49[1.22-1.82]), coma (5.12[1.70-15.38]). Long-term bed stay (5.84[5.12-6.66]), and healthcare-related risk factors such as chemotherapy (1.96[1.28-3.01]), haemodialysis (3.12[1.80-5.39]), hormone therapy (2.96[1.96-4.45]), immunosuppression (2.45[1.55-3.87]), and use of antibiotics (6.64 [3.16-13.96]), and longer than 15 hospitalisation days (13.36[6.80-26.26]) were also identified as significant risk factors. The second systematic review reported that the pooled median estimates for total medical expenditure, medicine expenditure and hospitalisation days per hospitalised patient with HAIs were ¥34,415.62, ¥20,065.21 and 34.01 days, respectively. As for the additional direct economic burden attributable to HAIs, the corresponding figures were ¥24,881.37, ¥9,438.46 and 13.89 days. In this selected hospital, the average annual HAIs prevalence was 0.68%, ranging from 0.57% to 0.83% over the study period. HAIs were significantly associated with the government-funded health insurance (aOR: 1.47[1.14-1.89]), S00-T98: Injury, poisoning and certain other consequences of external causes (1.83[1.37-2.45]), use of antibiotics (12.91[8.37-19.91]), invasive procedures (7.16, [5.67-9.04]), and surgery (2.47[1.98-3.09]). The additional direct economic burden attributable to HAIs per hospitalised patient was ¥17931.62 (total medical expenditure), ¥6,012.11 (medicine expenditure), ¥4,743.63 (out-of-pocket expenditure), ¥1,053.43 (antibiotics expenditure), and 15 days (hospitalisation days), while the corresponding figures were ¥7,727.68, ¥2,464.4, ¥1,598.01, ¥182.22, and 4 days in terms of the additional direct economic burden caused by AMR among HAIs hospitalised patients. Conclusions: This PhD thesis reported a relatively low HAIs prevalence over the study period in this Chinese general hospital, compared with existing evidence. It is necessary to establish real-time HAIs surveillance in Chinese hospitals to improve the identification of HAIs cases. The thesis emphasised the impact of the government-funded health insurance and the use of antibiotics on the occurrence of HAIs to some extent. Further research is needed to investigate how the government-funded health insurance affects the detection and treatment of HAIs. In this cross-sectional study, the additional direct economic burden attributable to HAIs was lower than that reported in the systematic review. However, this thesis demonstrated that HAIs with AMR bacteria resulted in a greater direct economic burden than HAIs alone. This is the first time such findings have been demonstrated within in a Chinese general hospital.