The performances of multilayer Hex-star phosphorene (HP) for the CO2 removal from natural gas were investigated by molecular simulation combined with real adsorbed solution theory (RAST). The influences of pressure (0.01–3.0 MPa), molar fraction of CO2 in bulk gas (0.05, 0.1, 0.2, 0.3, 0.4) and pre-adsorbed water content (0.0–9.9 mmol g−1) in adsorbents were thoroughly discussed at 300 K. The adsorption isotherms of both CO2 and CH4 predicted by RAST agree well with the simulation data. The adsorption selectivity calculations indicate that the multilayer HP exhibits an excellent separation performance under high pressure and high CO2 concentration. Meanwhile, under the low CO2 concentration, resulting from the sieving effect and stronger interactions between CO2 and water molecules, the CO2 selectivity can be significantly improved without impact of CO2 loading by pre-adsorbing some water molecules in the multilayer HP. This work suggests that the HP can act as a promising material for natural gas purification.