COVID-19 infections are returning to many countries because of the emergence of variants or declining antibody levels provided by vaccines. An additional dose of vaccination is recommended to be a considerable supplementary intervention. We aim to explore public acceptance of the third dose of the COVID-19 vaccine and related influencing factors in China. This nationwide cross-sectional study was conducted in the general population among 31 provinces in November, 2021. We collected information on basic characteristics, vaccination knowledge and attitudes, and vaccine-related health beliefs of the participants. Univariable and multivariable logistic regression models were used to assess factors associated with the acceptance of a third COVID-19 vaccine. A total of 93.7% (95% CI: 92.9–94.6%) of 3119 Chinese residents were willing to receive a third dose of the COVID-19 vaccine. Individuals with low level of perceived susceptibility, perceived benefit, cues to action cues, and high level of perceived barriers, old age, low educational level, low monthly household income, and low knowledge score on COVID-19 were less likely to have the acceptance of a third dose of COVID-19 (all p < 0.05). In the multivariable logistic regression model, acceptance of the third dose of COVID-19 vaccine was mainly related to previous vaccination history [Sinopharm BBIP (aOR = 6.55, 95% CI 3.30–12.98), Sinovac (aOR = 5.22, 95% CI:2.72–10.02), Convidecia (aOR = 5.80, 95% CI: 2.04–16.48)], high level of perceived susceptibility (aOR = 2.48, 95% CI: 1.48–4.31) and high level of action cues (aOR = 23.66, 95% CI: 9.97–56.23). Overall, residents in China showed a high willingness to accept the third dose of COVID-19 vaccines, which can help vaccine manufacturers in China to manage the vaccine production and distribution for the huge domestic and international vaccine demand. Relevant institutions could increase people’s willingness to booster shots by increasing initial COVID-19 vaccination rates, public’s perception of COVID-19 susceptibility and cues to action through various strategies and channels. Meanwhile, it also has certain reference significance for other countries to formulate vaccine promotion strategies.