In order to study the characteristics of tectonic subsidence and its main controlling factors of Kaiping Sag in Pearl River Mouth Basin, based on the latest interpretation results of two seismic sections, 43 virtual wells were selected on the two seismic sections to calculate the tectonic subsidence and conduct a comprehensive analysis. The results show that: (1) The tectonic subsidence of Kaiping Sag is large at the rifting stage (49-30 Ma), and the tectonic subsidence of each sag is quite different. The tectonic subsidence is relatively small at the post-rifting stage (30 Ma to present), and the differences of tectonic subsidence in each sub-sag are small. (2) The first episode of the rift stage (deposition period of Wenchang Formation, 49-39 Ma) was the period of maximum tectonic subsidence. The tectonic subsidence rate decreases significantly in the second episode of the rift stage (deposition period of Enping formation, 39-30 Ma). The tectonic subsidence increases in varying degrees in the drift period (30-17.5 Ma) and Neotectonic Movement period (after 17.5 Ma). (3) Differential subsidence is a basic feature of Kaiping sag, and the multi-stage tectonic movement and segmented and differential activities of detachment fault are the major factors of differential subsidence in Kaiping Sag.