Abstract: The Paleozoic marine strata series in the middle Yangtze area is basically similar to that of the upper Yangtze area. However, no substantial results have been achieved over a long and tortuous exploration period. This paper studies and analyzes regional structures, sedimentary development, hydrocarbon source rock, reservoir sedimentation belts and reservoir-cap assemblages in the middle Yangtze area. It concludes that two main potential exploration targets exist in the middle Yangtze area – the lower one composed of Sinian System and Cambrian Systen and the upper one composed of Permian System and Triassic System. This area has the desirable petroleum geological conditions for discovery of conventional natural gas and shale gas with great resources potential. It is supposed to be a key potential area for natural gas exploration. It is proposed that the effective exploration areas of the upper target include Shizhu complex syncline located from West Hubei to East Chongqing, Tuditang and Dangyang synclinorium on Jianghan Plain, and the southern part of Lichuan synclinorium in West Hunan-Hubei area. The effective exploration areas of the lower target include Shizhu complex syncline from West Hubei to East Chongqing and favorable zones in West Hunan-Hubei area. The Cambrian Niutitang Formation in West Hunan-Hubei area is the favorable zone for shale gas exploration while the Jiangzhi-Dangyang block is the favorable zone for shale gas exploration of Ordovician Wufeng Formation – Silurian Longmaxi Formation. The exploration principles should be focused on structural development and accumulation process, highlighting evaluation of reservoirs and preservation, putting the same emphasis on both conventional and unconventional oil and gas, and strengthening technological research to make breakthroughs in marine exploration of the middle Yangtze area.