A compact and accurate primary reference fuel (PRF) mechanism which consists of 46 species and 144 reactions was developed and validated to consider the fuel chemistry in combustion simulation based on a homogeneous charged compression ignition (HCCI) mechanism. Some significant reactions were updated to ensure its capabilities for predicting combustion characteristics of PRFs. To better predict the laminar flame speed, the relevant C2–C3 carbon reactions were coupled in. This enhanced PRF mechanism was validated by available experimental data references including ignition delay times, laminar flame speed, premixed flame species concentrations in jet stirred reactor (JSR), rapid compression machine (RCM), and shock tube. The predicted data was calculated by chemkin-ii codes. All the comparisons between experimental and calculated data indicated high accuracy of this mechanism to capture combustion characteristics. Also, this mechanism was integrated into kiva4–chemkin. The engine simulation data (including in-cylinder pressure and apparent heat release rate (HRR)) was compared with experimental data in PRF HCCI, partially premixed compression ignition (PCCI), and diesel/gasoline dual-fuel engine combustion data. The comparison results implied that this mechanism could predict PRF and gasoline/diesel combustion in computational fluid dynamic (CFD) engine simulations. The overall results show this PRF mechanism could predict the conventional fuel combustion characteristics in engine simulation.