On-board fuel reforming offers a prospective clean combustion mode for the engines. The flexible cylinder engine strategy (FCE) is a new kind of such mode. In this paper, the combustion of the primary reference fuel of PRF90 was theoretically investigated in a homogeneous charge compression ignition engine to validate the FCE mode, mainly focusing on the ignition delay time, the flame speed, and the emissions. The simulations were performed by using the Chemkin2.0 package to demonstrate the fuel reforming process, the cooling effect on the reformed fuel, and the combustions of the mixture of the fresh fuel and the reformed fuel in the normal cylinders. It was found that the FCE mode decreased the ignition delay time of the fuel by about 35 crank angles at a typical engine condition. The reaction pathways analyses indicated that methyl peroxide (CH3OOH), ketohydroperoxides (KETs), and hydrogen peroxide (H2O2) were the key species to decrease the ignition delay time among the reformed species, while the addition of acetone and formaldehyde resulted in misfire in the normal cylinders. The FCE combustion mode increased the laminar flame speed of the fuel at 1 atm and 50 atm, respectively, with hydrogen and carbon monoxide being the key species. Finally, the FCE combustion mode decreased the harmful emissions, such as 1,3-butadiene and formaldehyde. The reaction pathway analyses indicated that the reaction pathways were altered by the addition of the reformed species. The concentrations of the concerned emissions were also altered as the result. This work demonstrated that the FCE mode is a potential clean combustion mode.