The presented paper aims to study the influence of mineral diesel fuel and synthetic Gas-To-Liquid fuel (GTL) on the injection process, fuel flow conditions, and cavitation formation in a modern common-rail injector. First, the influence on injection characteristics was studied experimentally using an injection system test bench, and numerically using the one-dimensional computational program. Afterward, the influence of fuel properties on internal fuel flow was studied numerically using a computational program. The flow inside the injector was considered as multiphase flow and was calculated through unsteady Computational Fluid Dynamics simulations using a Eulerian–Eulerian two-fluid approach. Finally, the influence of in-cylinder back pressure on the internal nozzle flow was studied at three distinctive back pressures. The obtained numerical results for injection characteristics show good agreement with the experimental ones. The results of 3D simulations indicate that differences in fuel properties influence internal fuel flow and cavitation inception. The location of cavitation formation is the same for both fuels. The cavitation formation is triggered regardless of fuel properties. The size of the cavitation area is influenced by fuel properties and also from in-cylinder back pressure. Higher values of back pressure induce smaller areas of cavitation and vice versa. Comparing the conditions at injection hole exit, diesel fuel proved slightly higher average mass flow rate and velocities, which can be attributed to differences in fluid densities and viscosities. Overall, the obtained results indicate that when considering the injection process and internal nozzle flow, GTL fuel can be used in common-rail injection systems with solenoid injectors.