Due to energy shortages and environmental issues, the application of reactivity controlled compression ignition (RCCI) combustion in internal combustion engines has received extensive attention. Through the verification of the model, RCCI combustion can be accurately simulated. In this study, the combustion and the emission performance of a single-cylinder heavy-duty natural gas/diesel RCCI engine have been optimized through numerical simulation. Six important parameters including start of injection (SOI) timing, intake valve closing temperature, intake valve closing pressure, exhaust gas recirculation (EGR), swirl ratio, and spray angle have been investigated. The goal is to meet the requirements of European VI emission regulations while maintaining a high gross indicated efficiency (GIE). A strategy to achieve clean and efficient combustion of RCCI engine is proposed. The results showed that the addition of EGR can effectively reduce nitrogen oxide (NOx) emissions. SOI had the greatest impact on RCCI combustion and emission performance. Earlier SOI can improve the uniformity of the fuel mixture in the cylinder. Under the combined optimization of six important parameters, NOx, hydrocarbons, and carbon monoxide emissions can meet European VI emission regulations, and fuel consumption can meet Environmental Protection Agency consumption regulations, improving the GIE.