Background To investigate the willingness of female sex workers in urban entertainment venues in Guangxi, China to vaccinate against HPV and its influencing factors. Methods From August 15 to October 15, 2022, the intentional sampling method was used to select female sex workers in commercial sex trading entertainment venues in an urban area of Guangxi as the respondents of the study for the questionnaire survey. The questionnaire based on the information-motivation-behavior skills (IMB) model collected the basic information, HPV and HPV vaccine-related information and cognition, vaccination motivation, behavioral skills, and willingness to vaccination of the respondents. A multi-factor logistic regression model was used to analyze the influencing factors of the HPV vaccination willingness of the respondents. Results Among the 921 respondents, 712 (77.31%) were willing to receive HPV vaccination. The higher the level of awareness of HPV and HPV vaccine-related information, the stronger the motivation for HPV and HPV vaccination, and the higher the behavioral skills score, the higher the willingness of female sex workers in entertainment venues to receive HPV vaccination (P < 0.001). Female sex workers in entertainment venues with lower grades [OR(95% CI) = 0.693 (0.539, 0.891), P = 0.004] were more reluctant to receive HPV vaccination; those who favored the vaccines as effective in preventing disease [OR(95% CI) = 2.144 (1.449, 3.174), P < 0.001], had heard of HPV vaccine [OR( 95% CI) = 2.105 (1.451, 3.054), p < 0.001], being able to perceive the benefits of HPV vaccination [OR(95% CI) = 1.134 (1.045, 1.230), p = 0.002] and acquiring more behavioral skills i.e. self-decision for HPV vaccination [OR(95% CI) = 1.130 (1.008, 1.267), P = 0.036] and self-efficacy [OR (95% CI) = 1.135 (1.081, 1.191), P < 0.001] preferred to receive HPV vaccination. Conclusion Female sex workers in urban entertainment venues in Guangxi, China, have relatively high willingness to vaccinate against HPV, and should focus on introducing the benefits of primary prevention measures such as HPV vaccine to individuals and behavioral skills of HPV vaccination, so as to improve the willingness and vaccination rate of HPV vaccine.