To ensure the engineering safety of hydrate exploitation is the key and prerequisite for the commercial exploitation of solid-fluidization exploitation of natural gas hydrate in South China Sea. In order to study the influence of drilling parameters on multiphase flow characteristics and engineering safety in solid-fluidization of natural gas hydrate, a wellbore multiphase flow model considering thermal decomposition of hydrate was established and the influence of drilling parameters on engineering safety was analyzed. On that basis, the concrete parameter selection method to ensure the engineering safety were proposed. Results showed that, in order to ensure the safety of the solid- fluidization exploitation of natural gas hydrate, the displacement should be controlled between 40 L/s-50 L/s; If the geothermal gradient is higher than 0.04℃/m, drilling fluid should be cooled in advance; Drilling fluid density should be controlled between 1.20 g/cm3 and 1.25 g/cm3; In order to maximize the efficiency of hydrate extraction, the drilling rate should be maintained at about 20m/h. The result of this study could provide profound theoretical bases and valuable technical guidance for the Solid-fluidization commercial exploitation of natural gas hydrate in South China Sea.