Influenza vaccination is an important prevention strategy for flu illness. However, the vaccination rate is still low in Guangzhou, China. This study aimed to understand the status of knowledge, the attitude towards the vaccines' reliability and safety, and other aspects associated with the willingness and practice of influenza vaccines in the pediatric and adult populations of Guangzhou city. This study was performed in eleven districts in Guangzhou between November 2020 and December 2020, including the Yuexiu, Liwan, Haizhu, Tianhe, Baiyun, Panyu, Huadu, Nansha, Huangpu, Zengcheng, and Conghua districts. The parents of children and teenagers under the age of eighteen in Guangzhou were surveyed using self-administered questionnaires in four domains: demographic information, the knowledge status and perception of influenza vaccination, the willingness and attitude towards influenza vaccination, and previous vaccine uptake. A multivariable logistic regression was employed to assess the possible determinants of willingness and practice to receive influenza vaccination, calculating the odds ratios (ORs) and 95% confidence interval (CI). A two-sided p-value < 0.05 was deemed statistically significant. A total of 13,213 valid questionnaires were collected (validity rate 98.8%). Out of these participants, 42.62% (5631 participants) expressed a willingness to receive the influenza vaccine, while 55.40% (7320 participants) reported that their children and teenagers had been vaccinated against the flu. Furthermore, 40.44% of the respondents (5343 participants) or other family members had received the influenza vaccine. Logistic regression indicated that factors such as being female (OR = 1.395, 95% CI: 1.278-1.522), being involved in the work of COVID-19 prevention and control (1.551, 1.396-1.724), affirming the preventive effects of vaccination (2.474, 2.106-2.906), knowing about annual influenza vaccination (2.756, 2.540-2.992), and understanding prioritized influenza vaccination populations (1.464, 1.343-1.596) were all positively associated with vaccination willingness. Conversely, middle-aged persons (aged 40-49 years old) (0.726, 0.617-0.853), higher educational levels (undergraduate versus middle school) (0.858, 0.768-0.959), heightened concerns about vaccine safety (considering side effects are obvious versus considering it is safe and basically no side effects) (0.284, 0.188-0.429) and lower knowledge scores (0.813, 0.701-0.942) were adversely linked with vaccination willingness. These findings provide essential insights for altering the perception of influence and influenza vaccination, as well as enhancing health communication strategies to improve influenza vaccine uptake among Guangzhou residents.