COVID-19 vaccine hesitancy remains prevalent globally. However, national data on this issue in the general population after the termination of the zero-COVID policy in China are limited. In March 2023, we conducted a nationwide cross-sectional survey among Chinese adults using a self-administered questionnaire. Descriptive statistics and multivariate logistic regressions were employed. Among 4,966 participants, 43.8% reported COVID-19 vaccine hesitancy following the end of the zero-COVID policy in China. Higher rates of vaccine hesitancy were associated with being married (married: OR 1.36, 95%CI 1.17-1.57; other marital status: OR 1.86, 95%CI 1.36-2.55), working in healthcare (OR 1.64, 95%CI 1.38-1.96), having both minors and older adults in the household (OR 1.45, 95%CI 1.20-1.75), having no minors and older adults in the household (OR 1.44, 95%CI 1.17-1.77), having chronic diseases (OR 1.42, 95%CI 1.23-1.64), experiencing adverse events post-vaccination (OR 1.39, 95%CI 1.19-1.61), and uncertainty about previous COVID-19 infection (OR 1.45, 95%CI 1.13-1.86). Conversely, participants who had received the influenza vaccine in the past three years (OR 0.62, 95%CI 0.54-0.72), had previously taken the COVID-19 vaccine (OR 0.44, 95%CI 0.32-0.59), and had higher confidence in vaccines (OR 0.63, 95%CI 0.60-0.67) were less likely to exhibit hesitancy. Our findings indicate a significant level of vaccine hesitancy, underscoring the urgent need for tailored public health strategies to address vaccine hesitancy and improve uptake post-zero-COVID policy in China. A comprehensive understanding of public concerns and related factors is essential for developing effective vaccine communication strategies.