Introduction Since 2017, pre-exposure prophylaxis (PrEP) has been one of the tools in combination HIV prevention strategies. The objective of our questionnaire was to analyze the knowledge and the position of general practitioners in Hauts-de-France on PrEP. Method This quantitative, observational, cross-sectional study was conducted in 2020 using an anonymous questionnaire sent by post to a sample of 3007 GPs. Results Four hundred and forty-four questionnaires (14.8 %) were included. The GPs were predominantly male (n = 253, 57 %) with a median age of 47 years. The median interest shown by respondents was 7/10. One hundred and sixty participating GPs (36%) were aware of the principles of PrEP, one hundred and sixty were only aware of the title (36%) and 124 (28%) showed no awareness at all. Out of the 160 GPs who knew about PrEP, 72 % considered it effective, 30 % knew about it from a patient and 34 % declared having at least one patient using PrEP. GPs who knew about PrEP were more likely to: have graduated less than 10 years before, having seen in consultation men who have sex with men (MSMs) and, lastly; using screening practices for sexually transmitted infections that were better aligned with the recommendations than those who reported not knowing about PrEP. Conclusion Although PrEP remains insufficiently known to GPs, many expressed eagerness to be involved. The training of health professionals and the highlighting of GPs’ role in prevention could help to optimize the fight against HIV.