Several NE-striking sedimentary basins, including the representative Pearl River Mouth Basin, formed under a unified tectonic stress regime in the northern continental margin of the South China Sea during the Cenozoic. Studying the tectonic stress regime of the Pearl River Mouth Basin can provide constraints on the expansion and evolution of the South China Sea. Based on the analysis of high-precision 2D and 3D seismic data, the following results were obtained. (1) The T80 reflection interface (40 Ma) is an important unconformity interface and corresponds to a transformation in the tectonic stress regime. (2) From 40 Ma to 10.5 Ma (T80-T32 reflection interface), the Pearl River Mouth Basin was under an extensional tectonic stress regime with a N-S extensional direction. According to the research results of basins in the north of the South China Sea, a new tectonic evolution model of the South China Sea has been established, in which the South China Sea Oceanic Basin is deemed to have formed through approximately N-S extension under pre-existing tectonic conditions during 40-15.5 Ma. The new model is supported by the seawater depth and the seafloor geomorphy in the South China Sea Ocean Basin.