Background: Vaccination is the most effective method for the prevention of COVID-19. However, willingness to be vaccinated is not consistent. This study aimed to explore vaccine cognition, risk perception, and health behavior of COVID-19 in China. Methods: A cross-sectional survey was performed in Guangdong province, China, including demographic characteristics, health status and preventive behaviors, cognition of COVID-19 vaccination, and the health belief model (HBM). Results: A total of 1640 participants were recruited. The main access to information about COVID-19 and vaccination as through official news and broadcasts (67.3%), social network software (58.7%), and professional popularization (46.2%). The precautions taken were wearing a mask (67.0%) and avoiding gathering together (71.3%). COVID-19 vaccination acceptability was different among different age groups and educational levels (p < 0.001). The major reasons for accepting vaccination included that it was an effective way to prevent COVID-19 (61.8%) and that it was required by working units/schools (51.1%). The fitting effect indexes of the (HBM) Model 2 showed better fitting than those of Model 1. In Model 2, perceived benefits (OR = 3.13, 95% CI: 1.79−5.47), cues to action (OR = 2.23, 95% CI: 1.60−3.11), and different occupations (OR = 1.13, 95% CI: 1.04−1.23) were positively correlated with vaccine acceptance; while perceived susceptibility (OR = 0.47, 95% CI: 0.30−0.74) and perceived barriers (OR = 0.44, 95% CI: 0.29−0.69) were negative factors associated with vaccine acceptance. Conclusion: Different sociodemographic characteristics lead to differences in acceptance of vaccination, and the publicity and credibility of government play an indispensable role in epidemic control. The establishment of the HBM further predicted that perceived susceptibility to COVID-19, benefits of vaccination, barriers of cognition, and cue to action were the influencing factors of intention and health behaviors.