During the drilling and development of high CO2 gas field, due to the high solubility of CO2 containing natural gas in drilling fluid, the gas invasion has "concealment" and "sudden" of later expansion, resulting in well control accidents. Therefore, it is of great significance to study the solubility of high CO2 gas and the law of multiphase flow in annulus after gas invasion. In this paper, the multiphase flow equations considering gas dissolution are established. The solubility of CO2 + CH4 in aqueous solution is measured by phase equilibrium experimental device. According to the experimental results, the auxiliary equation suitable for the solubility prediction of CO2 containing natural gas is optimized. It is found that the fugacity activity method using SRK equation of state is the best. By analyzing the law of multiphase flow through specific examples, it is found that considering the influence of gas solubility, the increment of mud pit changes slowly, the expansion and precipitation of intrusive gas is close to the wellhead, and the expansion burst is stronger. When the CO2 content of intrusive gas is higher, the time of incremental change of mud pit monitored on the ground is prolonged, and the concealment is further increased, which is more harmful to the safety control of wellbore pressure.