Abstract: Marine shale in Lower Cambrian Niutitang Formation of northwestern Hunan, with high thermal maturity, experienced multi-period structural movement in geologic history, resulting in challenges on selecting the favorable areas of shale gas. The influencing factors of shale gas exploitation potential were investigated. Four second-order indices, including formation conditions, reservoir conditions, storage conditions and integrated matching conditions, and their corresponding third-order indices for assessment of the shale gas exploitation potential were established. The weight values of all second and third-order indices were determined by the fuzzy mathematics and the multi-layered fuzzy mathematics model for evaluation of shale gas exploration potential were set up. The multi-layered fuzzy mathematics model was applied to evaluate comprehensively the exploration potential of shale gas in the third-order tectonic units, including Hefeng anticlinorium, Sangzhi synclinorium, Guzhang uplift, Yuanma basin and Dongting depression. The results showed that Sangzhi synclinorium has the best potential for shale gas exploitation, followed by Hefeng anticlinorium. The assessment system established can be regarded as a reference model in shale gas exploitation potential assessment of shale gas with high thermal maturity and complex geological structures.