It is well known that in-nozzle flow behavior can significantly influence the near-nozzle spray formation and mixing that in turn affect engine performance and emissions. This in-nozzle flow behavior can, in turn, be significantly influenced by fuel properties. The goal of this study is to characterize the behavior of two different fuels, namely, a straight-run naphtha that has an anti-knock index of 58 (denoted as “Full-Range Naphtha”) and n-dodecane, in a simulated multi-hole common-rail diesel fuel injector. Simulations were carried out using a fully compressible multi-phase flow representation based on the mixture model assumption with the Volume of Fluid method. Our previous studies have shown that the characteristics of internal and near-nozzle flow are strongly related to needle motion in both the along- and off-axis directions. A robust computational fluid dynamics setup was first developed, accounting for needle motion, and validated against experimental data for n-dodecane fuel. Detailed simulations revealed the influence of fuel properties on the propensity for cavitation for both fuels. The two fuels were compared with respect to global parameters such as mass flow rate at the orifice exit and area contraction coefficients, and local parameters such as velocity distribution inside the sac and orifices. Parametric investigations were also performed to understand the influence of injection pressure and temperature, and geometry effects on both fuels. Owing to its higher saturation pressure, Full-Range Naphtha was observed to cavitate more than n-dodecane across all the investigated conditions. Although Full-Range Naphtha has a lower density than n-dodecane, owing to its lower viscosity, the mass flow rates of both fuels at the nozzle exit were comparable. The authors also observed that the fuel propensity for cavitation could locally influence the flow structures and enhance or dampen their evolution. This observation may have a profound influence in the needle seat region, wherein at low needle lift, under choked conditions, enhanced cavitation was observed with the Full-Range Naphtha.