<p>Natural gas residual pressure energy is abundant, and utilizing this energy to drive turbine rotation for power generation is a key technology in residual pressure energy utilization. To enhance the output performance of the turbine used in single-well natural gas residual pressure power generation, this study adopted a dynamic mesh model combined with fluid simulation methods to optimize the turbine’s structural parameters based on the response surface methodology. Parametric modeling was employed to conduct numerical analysis of the single-stage turbine under initial conditions, thereby obtaining its baseline performance parameters. On this basis, a single-factor analysis was performed on four parameters—leading-edge radius, trailing-edge radius, blade number, and axial clearance—to investigate their influence on turbine output efficiency and power. Taking the optimal combination of power and efficiency as the optimization objective, a multi-objective optimization study was carried out using the Box-Behnken response surface method to examine the effects of multi-factor interactions on performance parameters. The results indicate that the optimal blade parameter combination significantly improves turbine output power and conversion efficiency. Compared with the original design, the optimized turbine achieves a 33.4 % increase in output power and a 1.85 % improvement in efficiency. The optimization of turbine structural parameters can substantially enhance the output performance of a single-stage turbine, providing critical technical support for the development of a prototype turbine power generation device driven by residual pressure.</p>