The urban heat island (UHI) effect exacerbates the adverse impact of heat on human health. However, while the UHI effect is further intensified during extreme heat events, prior studies have rarely mapped the UHI effect during extreme heat events to assess its direct temperature impact on mortality. This study examined the UHI effect during extreme heat and non-extreme heat scenarios and compared their temperature-mortality associations in Hong Kong from 2010 to 2019. Four urban heat island degree hour (UHIdh) scenarios were mapped onto Hong Kong’s tertiary planning units and classified into three levels (Low, Moderate, and High). We assessed the association between temperature and non-external mortality of populations living in each UHIdh level for the extreme heat/non-extreme heat scenarios during the 2010–2019 hot seasons. Our results showed substantial differences between the temperature-mortality associations in the three levels under the UHIdh extreme heat scenario (UHIdh_EH). While there was no evidence of increased mortality in Low UHIdh_EH areas, the mortality risk in Moderate and High UHIdh_EH areas were significantly increased during periods of hot temperature, with the High UHIdh_EH areas displaying almost double the risk (RR: 1.08, 95%CI: 1.03, 1.14 vs. RR: 1.05, 95 % CI: 1.01, 1.09). However, other non-extreme heat UHI scenarios did not demonstrate as prominent of a difference. When stratified by age, the heat effects were found in Moderate and High UHIdh_EH among the elderly aged 75 and above. Our study found a difference in the temperature-mortality associations based on UHI intensity and potential heat vulnerability of populations during extreme heat events. Preventive measures should be taken to mitigate heat especially in urban areas with high UHI intensity during extreme heat events, with particular attention and support for those prone to heat vulnerability, such as the elderly and poorer populations.