Because there is neither waste rock nor mill tailings in the gypsum mine, and the buildings on the goaf of gypsum mine are needed to be protected, the research proposed the scheme of the clay filling technology. Gypsum, cement, lime and water glass were used as adhesive, and the strength of different material ratios were investigated in this study. The influence factors of clay strength were obtained in the order of cement, gypsum, water glass and lime. The results show that the cement content is the determinant influence factor, and gypsum has positive effects, while the water glass can enhance both clay strength and the fluidity of the filing slurry. Furthermore, combining chaotic optimization method with neural network, the optimal ratio of composite cementing agent was obtained. The results show that the optimal ratio of water glass, cement, lime and clay (in quality) is 1.17:6.74:4.17:87.92 in the process of bottom self-flow filling, while the optimal ratio is 1.78:9.58:4.71:83.93 for roof-contacted filling. A novel filling process to fill in gypsum mine goaf with clay is established. The engineering practice shows that the filling cost is low, thus, notable economic benefit is achieved. Because there is neither waste rock nor mill tailings in the gypsum mine, and the buildings on the goaf of gypsum mine are needed to be protected, the research proposed the scheme of the clay filling technology. Gypsum, cement, lime and water glass were used as adhesive, and the strength of different material ratios were investigated in this study. The influence factors of clay strength were obtained in the order of cement, gypsum, water glass and lime. and gypsum has positive effects, while the water glass can enhance both clay strength and the fluidity of the filing slurry. The results show that the optimal ratio of water glass, cement, lime and clay (in quality) is 1.17: 6.74: 4.17: 87.92 in the process of bottom self-flow filling, while the optimal ratio is 1.78: 9.58: 4.71: 83.93 A novel filling process to fill in gypsum mine goaf with clay is established. The engineering practice shows that the filling cost is low, thus, notable economic benefit is achieved.