High temperature in deep mines has become the main concern to limit the production capacity of mines. To mitigate the adverse impact of the underground high-temperature environment on mine production, an orthogonal test was used to design an experimental scheme, i.e., the contents of tailings, glass beads, and ordinary Portland cement PC32.5 (PC) were set as the main horizontal factors to prepare thermal insulation material samples with different combination ratios. Compressive strength and thermal conductivity were investigated, as well as the microstructure. Based on the response surface method (RSM), the interaction between the horizontal factors was explored and analyzed using Design Expert 12 software, and thus non-linear fitting equations were established with the volume fractions of the main horizontal factors as independent variables and compressive strength and thermal conductivity as dependent variables in the analysis parameters of thermal insulation materials. The results showed that errors between the fitted calculated values of compressive strength and thermal conductivity and the experimental results were only 0.42% and 1.2%, respectively, indicating that the process parameters obtained with the optimum fitting ratio under the established fitting equation are highly reliable and have excellent compressive strength and thermal insulation properties. The optimized results obtained by combining the orthogonal method and the RSM show accurate prediction and applicability in the field of thermal insulation materials in mines.