Objective: To analyze the quadrivalent influenza vaccine intention of 718 health care workers (HCWs) in the Pearl River Delta region from 2015 to 2017. Method: In May 2018, 718 HCWs from the department related to the diagnosis and treatment of influenza in 17 hospitals (6 tertiary hospitals, 5 secondary hospitals and 6 primary hospitals) from Guangzhou, Jiangmen, Zhuhai and Dongguan were selected by using stratified sampling method. Questionnaire survey and face-to-face interview were used to collect the information of influenza vaccination, the intention of the quadrivalent influenza vaccine, the acceptance of free and required vaccination policies, and recommendations for increasing influenza vaccination intentions from 2015 to 2017. The multivariate logistic regression was used to analyze factors associated with the vaccination intention. Results: A total of 718 HCWs were surveyed and 147 of them were interviewed face to face. Among them, the vaccination rate of primary hospitals [17.39%(40/230)] was higher than that of other hospitals (χ²=15.80, P<0.05). If the vaccine could be free, 84.82% (609/718) of HCWs would like to be vaccinated. The multivariate logistic regression showed that the factors, HCWs who were aged ≥50 years (OR=3.44, 95%CI:1.43-8.28), worked in department of prevention and health care (OR=2.35, 95%CI:1.16-4.75), learned about the quadrivalent influenza vaccine (OR=2.94, 95%CI:2.08-4.18), knowed that HCWs are priority (OR=2.33, 95%CI:1.56-3.48), and had a history of trivalent influenza vaccination from 2015 to 2017 (OR=4.70, 95%CI:3.08-7.15), were associated with the vaccination intention. Conclusion HCWs in the Pearl River Delta region had weak inclination of getting quadrivalent influenza vaccine. HCWs who were age (≥50 years old), worked in department of prevention and health care, learned about the quadrivalent influenza vaccine, knowed that HCWs are priority, and had a history of trivalent influenza vaccination from 2015 to 2017 were factors positively associated with the vaccination intention.