Abstract: The Panyu 4 Depression in the Pearl River Mouth Basin is rather small but rich in hydrocarbon, and the current proved geological reserves have exceeded the early-estimated geological resources. Lacking of source rock knowledges, especially lacking of accurate description of high-quality source rocks, may be the main reason that greatly limited the recognition of the exploration potential of the depression. Taking this difficult problem as the standpoint to seek for breakthrough, this paper uses the latest drilling and seismic data and adopts the unique perspective of sequence stratigraphy to systematically make prediction of source rocks in the depression. According to the various reflection characteristics identified from seismic data and the cyclic characteristics from drilling data, the Wenchang Formation in Panyu 4 Depression is divided into five third-order sequences, and the isochronous stratigraphic framework is then established. On this basis, the distribution area of high-quality source rocks in the third sequence of Wenchang Formation in Panyu 4 Depression is revealed by using the latest seismic sedimentology techniques. The results show that the area of high-quality source rocks in the Panyu 4 Depression is relatively wide, especially in the North Sub-depression and the West Sub-depression, the area of high-quality source rocks exceeds previous expectations. The research results of this paper may provide clues for oil and gas exploration in this region and the Pearl River Mouth Basin.