The urban heat island (UHI) effect has become a global issue, attracting widespread attention in recent years. Urban vegetation is an effective way to mitigate UHI through evapotranspiration (ET). However, the seasonal variation in vegetation cooling effect and its driving factors have not been well investigated. Therefore, the seasonal UHI intensity (UHII) on typical clear days in 2021 was calculated for Shenzhen based on the land surface temperature (LST) data from the Moderate Resolution Imaging Spectroradiometer (MODIS). The slope between UHII and vegetation coverage was then used to characterize the vegetation cooling effect. Results showed that: (1) there is a significant negative linear correlation between UHII and vegetation coverage, with slopes mostly less than −1 and coefficients of determination (R2) larger than 0.4. (2) The slopes varied seasonally, indicating a larger vegetation cooling effect during summer daytime. A 10 % increase in vegetation coverage can reduce the daytime UHII by 0.16 °C in January and 0.59 °C in June, while at nighttime, the cooling effect varied between 0.12 °C in January and 0.27 °C in June. The daytime and nighttime UHII for the whole year can be reduced by 0.43 °C and 0.24 °C, respectively. (3) The seasonal variation in vegetation cooling effects during the daytime can be largely explained by that of ET, which is mainly driven by leaf area index (LAI).