Taking the opposed multi-burner (OMB) coal water slurry (CWS) gasification system as the simulation object, based on the gasification process flow-path and the flow field distribution characteristics in the gasifier, the model of CWS gasification system is established by using the chemical simulation software UniSim Design, the simulation results are in good agreement with the industrial data. On this basis, the Morris method is used to analyze the sensitivity of gasification parameters, and the response surface between coal gasification performance index and sensitive parameters is constructed by using the response surface method. The sensitivity of different gasification parameters and the impact of key sensitive parameter interactions on gasification performance indicators is investigated. The results show that the gasification parameters have different sensitivities for different responses. When the operating temperature range of the gasifier is limited to 1212 degrees C to 1400 degrees C and the syngas water-gas ratio is in the range of 1.0 to 1.4, there is a safe boundary for oxygen-coal ratio and CWS concentration. In actual production, the relevant parameters should be avoided to deviate from the safety region. This article provides a reference for the safe and stable operation of actual industrial production.