Growing environmental concerns and demand for better fuel economy are driving forces that motivate the research for more advanced engines. Multi-mode combustion strategies have gained attention for their potential to provide high thermal efficiency and low emissions for light-duty applications. These strategies target optimizing the engine performance by correlating different combustion modes to load operating conditions. The extension from boosted SI mode at high loads to advanced compression ignition (ACI) mode at low loads can be achieved by increasing compression ratio and utilizing intake air heating. Further, in order to enable an accurate control of intake charge condition for ACI mode and rapid mode-switches, it is essential to gain fundamental insights into the autoignition process. Within the scope of ACI, homogeneous charge compression ignition (HCCI) mode is of significant interest. It is known for its potential benefits, operation at low fuel consumption, low NOx and PM emissions. In the present work, a virtual Cooperative Fuel Research (CFR) engine model is used to analyze fuel effects on ACI combustion. In particular, the effect of fuel Octane Sensitivity (S) (at constant RON) on autoignition propensity is assessed under beyond-RON (BRON) and beyond-MON (BMON) ACI conditions. The 3D CFR engine computational fluid dynamics (CFD) model employs finite-rate chemistry approach with multi-zone binning strategy to capture autoignition. Two binary blends with Research Octane Number (RON) of 90 are chosen for this study: Primary reference fuel (PRF) with S = 0, and toluene-heptane (TH) blend with S = 10.8, representing paraffinic and aromatic gasoline surrogates. Reduced mechanisms for these blends are generated from a detailed gasoline surrogate kinetic mechanism. Simulation results with the reduced mechanisms are validated against experimental data from an in-house CFR engine, with respect to in-cylinder pressure, heat release rate and combustion phasing. Thereafter, the sensitivity of combustion behavior to ACI operating condition (BRON vs BMON), air-fuel ratio (λ = 2 and 3), and engine speed (600 and 900rpm) is analyzed for both fuels. It is shown that the sensitivity of a fuel’s autoignition characteristics to λ and engine speed significantly differs at BRON and BMON conditions. Moreover, this sensitivity is found to vary among fuels, despite the same RON. This study also indicates that the octane index (OI) fails to capture the trend in the variation of autoignition propensity with S under BMON conditions.