As a core component in the gas transmission process, the internal wall surface of a gas pressure regulator is prone to failure due to long-term exposure to a high-pressure gas environment, resulting in poor reliability of the regulator. Thus, a thermo-hydro-mechanical coupling model for the FL gas pressure regulator is established in this paper, and the thermo-hydro-mechanical coupling results are verified by engineering data. The effect of valve opening on the parameters (temperature, deformation, and stress) of the gas pressure regulator is studied in detail through simulation. The results show that the stress is greater at the sleeve, valve bore, and outlet valve seat wall under the opening of 20% of the regulator. Finally, the response surface method is used to optimize the regulator to obtain a good fit and high predictive ability of the response surface equation. The optimal parameters for the gas pressure regulator are as follows: the wall thickness of the sleeve is 7.25 mm, the diameter of the valve bore is 25 mm, and the wall thickness of the outlet seat is 31.05 mm. The maximum equivalent stress with this combination of parameters is 135.62 MPa.