Background Alcohol screening and brief intervention (SBI) is an evidence-based intervention recommended by the World Health Organization. This study applied the Consolidated Framework for Implementation Research (CFIR) to understand facilitators and barriers of SBI implementation in primary care settings in Hong Kong, China.Methods This was a sequential mixed-method study. In-depth interviews of 21 physicians and 20 nurses working in the primary care settings from the public and private sectors were first conducted to identify CFIR constructs that were relevant to SBI implementation in the Chinese context and potential factors not covered by the CFIR. A questionnaire was then developed based on the qualitative findings to investigate factors associated with SBI implementation among 282 physicians and 295 nurses.Results The in-depth interviews identified 22 CFIR constructs that were facilitators or barriers of SBI implementation in Hong Kong. In addition, the stigmatization of alcohol dependence was a barrier and the belief that it was important for people to control the amount of alcohol intake in any situation was mentioned as a facilitator to implement SBI. In the survey, 22% of the participants implemented SBI in the past year. Factors associated with the SBI implementation echoed most of the qualitative findings. Among physicians and nurses in both sectors, they were more likely to implement SBI when perceiving stronger evidence supporting SBI, better knowledge and self-efficacy to implement SBI, more available resources, and clearer planning for SBI implementation in the clinics but less likely to do so when perceiving SBI implementation to be complicated and of higher cost, and drinking approved by the Chinese culture. Participants were more likely to implement SBI when perceiving SBI fit better with the existing practice and better leadership engagement in the public sector, but not in the private sector. Perceiving a stronger need and greater importance to implement SBI were associated with higher likelihood of SBI implementation among physicians, but not among nurses. Perceiving better organizational culture supporting SBI was positively associated with SBI implementation among nurses, but not among physicians.Conclusions There was a significant gap between SBI evidence and its implementation. Some strategies to improve SBI implementation may be different between physicians and nurses and between those in the public and private sectors. The CFIR is a useful framework for understanding facilitators and barriers of SBI implementation in primary care settings.