This work provides the target-oriented fuel design concept for efficient, clean combustion and identifies the functional configuration of fuel components for the homogeneous charge autoignition (HCAI) combustion mode. The n-heptanePODE(3)ethanol mixture is applied to exemplify the fuel design process. The interaction among n-heptane, PODE3, and ethanol for the heat release process and the role of PODE3 and ethanol on the soot precursors (n-C4H3, C2H2, C3H3, CH3, C2H4, and C4H4) reduction are also discussed. The main conclusions are summarized below: First, the 60% n-heptane20% PODE(3)20% ethanol exhibits distinct low temperature heat release, first high temperature heat release (HTHR) and second HTHR which are contributed by PODE3/n-heptane, n-heptane/ethanol, and ethanol, respectively. The dominant rate controlling reactions for OH accumulation are H atom abstraction from n-heptane and ketohydroperoxide decomposition of n-heptane. Therefore, n-heptane is the major ignition source, while PODE3 works as the auxiliary ignition source because the ignition process is mainly controlled by n-heptane. Second, both PODE3 and ethanol are free of n-C4H3 emission, and they can dramatically reduce the C2H2, C3H3, C2H4, and C4H4 emissions. Therein, PODE3 is more effective in C2H2, C2H4, and C4H4 reduction than ethanol. But PODE3 and ethanol both increase the CH3 production. Third, the functional configuration of fuel components for the HCAI combustion mode is chemical ignition sourcePM inhibitorhomogeneous charge (PM = particulate matter). The n-heptane, PODE3, and ethanol act as the chemical ignition source, PM inhibitor, and homogeneous charge, respectively, due to the high reactivity, the high oxygen mass content/lack of CC bond, and high volatility, respectively. The combustion temperature window of the HCAI combustion mode is 14002200 K, which corresponds to the CO/HC oxidation limit and NOx production limit, respectively.