Vaccine hesitancy is a major obstacle to the achievement of universal child vaccination, which has been studied extensively in Western countries but much less so in Asian countries, especially China. This cross-sectional survey is aimed to assess the prevalence of vaccine hesitancy and to explore the reasons for vaccine hesitancy among parents in Guangzhou. In January 2020, a questionnaire adapted to the Chinese setting from a widely-used hesitancy scale was administered to a sample of parents who brought their children aged <13 years to Community Health Service Centers for vaccination in Guangzhou. The incidence of vaccine hesitancy among those parents was 6.6% (50/755). Regression analysis showed that differences in socio-economic characteristics were not associated with the occurrence of vaccine hesitancy among parents in Guangzhou. However, strong distrust of domestic vaccine quality (OR = 10.9, 95% CI = 1.5–81.4), being required to have their children vaccinated for nursery and school entry (OR = 3.6, 95% CI = 1.7–7.7), and not being aware of which vaccines are officially required and which are optional (OR = 2.1, 95% CI = 1.1–4.3) were the risk factors significantly associated with vaccine hesitancy. In order to increase parents’ trust in domestic vaccine quality and reduce the prevalence of vaccine hesitancy, it is essential to strengthen quality control in domestic vaccine manufacturing and to proactively disseminate clear and accurate information about vaccines to parents. Furthermore, advocating the value of vaccination among all citizens of Guangzhou is crucial.