Objective: To analyze the epidemiological characteristics and spatial-temporal clustering of influenza in Lishui City, Zhejiang Province from 2016 to 2025, so as to provide a reference for formulating regional influenza prevention and control strategies. Methods: Data on influenza cases in Lishui City from 2016 to 2025 were collected from the Infectious Disease Reporting Information System of China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the temporal, population and regional distribution characteristics of influenza. The concentration ratio (M) method was used to evaluate seasonality. Spatial autocorrelation and spatial-temporal scan analysis were used to explore the spatial-temporal clustering. Results: A total of 192 016 influenza cases were reported in Lishui City from 2016 to 2025, with an average annual reported incidence of 774.32/105, showing an overall upward trend (P<0.05). The incidence peaked from November to March of the following year, indicating strong seasonality (M=0.661). There were 99 513 males and 92 503 females, with a male-to-female ratio of 1.08∶1. The majority of cases were aged 5-<15 years and were students, with 86 766 and 82 286 cases, accounting for 45.19% and 42.85%, respectively. The average annual reported incidence of influenza was relatively high in Songyang County, Jingning She Autonomous County and Yunhe County, with 1 255.22/105, 1 176.23/105 and 1 129.76/105, respectively. Spatial autocorrelation analysis showed a positive spatial correlation of influenza incidence in Lishui City from 2016 to 2025 (all P<0.05). From 2016 to 2018, the high-high clusters were mainly distributed in the northeastern region, while from 2019 to 2025, mainly distributed in the central and southern regions. Spatial-temporal scan analysis showed that the Class Ⅰ cluster was centered on Yuanhe Subdistrict in Yunhe County, covering Liandu District, Yunhe County, and Songyang County in the central region, as well as Jingning She Autonomous County and Longquan City in the southern region, involving 54 towns (subdistricts), with the clustering period from March 2023 to December 2025. Conclusions From 2016 to 2025, the reported incidence of influenza in Lishui City showed an upward trend, with a peak in winter and spring and strong seasonality. Children and adolescents aged 5-<15 years and students were identified as high-incidence populations. The incidence showed spatial-temporal clustering, with the central and southern regions being high-incidence areas.