Objective To explore the application methods and values of using health failure mode and effect analysis (HFMEA) to prevent surgical site infection (SSI) in patients undergoing bone fracture and craniotomy surgery with class Ⅰ incision. Methods Patients undergoing bone fracture and craniotomy surgery with class Ⅰ incision at the Chengdu Pidu District People’s Hospital between January 2020 to December 2021 were selected. Based on whether receiving HFMEA-based risk management or not, the patients were divided into conventional group and intervention group. The compliance rates with infection control measures, changes in risk priority numbers (RPN) at various stages (1 month and 10 months after intervention) of HFMEA implementation, and the incidence of SSI between the conventional group and the intervention group were compared. Results A total of 884 surgeries were included. Among them, there were 399 cases in the conventional group and 485 cases in the intervention group; 16 cases SSI occurred. A total of 7 SSI prevention and control measures had been formulated. Except for proper surgical attire (P＞0.05), there were statistically significant differences in the compliance rate of the other prevention and control measures between the two groups of patients (P＜0.05). In the intervention group, the RPN values of pre-operative, intra-operative, and post-operative risk factors at the 10th month after intervention were all lower than those at the 1st month after intervention (P<0.05). Except for the incidence of SSI during craniotomy surgery (6.1% vs. 1.8%, P=0.375), there were statistically significant differences in the total SSI incidence (3.3% vs. 0.6%) and bone fracture surgery SSI incidence (2.7% vs. 0.5%) between the conventional group and the intervention group (P>0.05). Conclusion Applying HFMEA-based risk management techniques to prospectively identify, assess, analyze, manage and track the risk of SSI in bone fracture and craniotomy surgery with class Ⅰ incision can effectively enhance the adherence of preventive measures and reduce the incidence rate of SSI.