Background The situation of the COVID-19 outbreak in the border areas of China and Vietnam is complex, and its progress may affect the willingness of urban and rural residents to receive the vaccine. Objective This study aims to understand the influence of the COVID-19 epidemic situation on the willingness of urban and rural residents in China-Vietnam border areas to get vaccinated and the factors that affect the vaccinations. Methods A cross-sectional survey was conducted in Hani-Yi Autonomous Prefecture of Honghe, a border area between China and Vietnam, using online and paper questionnaires from April 1 to June 4, 2021. A total of 8849 valid questionnaires were surveyed to compare the differences in the willingness of urban and rural residents to receive the COVID-19 vaccine. Single factor analysis and multivariate logistic regression analysis were used to explore the influence of the epidemic situation on the willingness to be vaccinated. Results In the border areas between China and Vietnam in Yunnan Province, both urban and rural residents had a high willingness (> 90%) to receive the COVID-19 vaccination, with a higher level of willingness in urban than in rural areas and a higher willingness among residents aged ≥ 56 years. Rural residents mainly concerned about the vaccination were different from urban residents (p< 0.05). About 54.8% of urban respondents and 59.2% of rural respondents indicated that their willingness to get COVID-19 vaccine would be affected by new COVID-19 cases. Respondents who were divorced, had an occupation other than farming, had contraindications to vaccination, were concerned about the safety of vaccines and worried about virus mutation, thought that the epidemic situation would not affect their willingness to get vaccinated (p< 0.05). Conclusion The prevention and control of epidemics in border areas is of considerable importance. It is necessary to conduct targeted health education and vaccine knowledge popularization among urban and rural residents to increase the vaccination rate and consolidate the epidemic prevention and control at the border.