Multi-dimensional models coupled with a detailed chemical mechanism were used to investigate the effect of fuel property on the exergy destruction due to chemical reaction in a reactivity controlled compression ignition (RCCI) engine. It is found that the exergy destruction due to the chemical reaction of methanol/diesel RCCI is lower than that of gasoline/diesel RCCI at the same combustion phasing. Since methanol addition has a negative effect on the low temperature heat release (LTHR) of diesel, the exergy destruction accumulation from LTHR to high temperature heat release (HTHR) in gasoline/diesel RCCI can be avoided in methanol/diesel RCCI resulted from the lower exergy destruction. Moreover, the combustion temperature in methanol/diesel RCCI is higher compared to gasoline/diesel RCCI, which is also beneficial to the lower exergy destruction. From the further analysis in a perfectly stirred reactor, when equivalence ratio is below the stoichiometric ratio, the difference of the exergy destruction due to the chemical reaction among the three fuels is insignificant, while the effect of combustion temperature is dominant. It is concluded that the exergy destruction during chemical reaction mainly derives from the C0-C1 reactions instead of the fuel decomposition from large molecule to small molecule. Although the chemical mechanism of C0-C1 is similar for different fuels, the unique combustion characteristics of methanol/diesel mixture improve both the LTHR behavior and the combustion temperature, which results in the lower exergy destruction.