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 in the flexible cylinder, the cooling effect on the reformed products, and the combustions of the mixture of the fresh fuel and the reformed products 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 in the reformed products, while the addition of acetone (CH3COCH3) and formaldehyde (CH2O) resulted in misfire in the normal cylinders. The FCE combustion mode increased the laminar flame speed of PRF90 both at 1 atm and 50 atm, with hydrogen (H2) being the key species. Finally, the FCE combustion mode decreased the harmful emissions significantly, such as acetylene (C2H2), ethylene (C2H4), propyne (C3H4), propene (C3H6),1,3-butadiene (1,3-C4H6), and CH2O. The reaction pathway analyses indicated that the reaction pathways were altered by the addition of the reformed species. This work demonstrated that the FCE mode is a potential clean combustion mode.