Hydrogen-fueled internal combustion engines (ICEs) exploiting exhaust gas recirculation (EGR) and lean-boosted combustion can be a viable solution to abate all criteria pollutants while simultaneously almost zeroing tailpipe CO2. However, the optimization of hydrogen-fueled ICE to fully exploit the fuel’s potential is a challenging task considering its characteristics, that on one side make hydrogen a desirable fuel for the future generation of ICEs, and on the other side are responsible for the risk of abnormal combustion. Therefore, the development of a simulation tool capable to predict the H2 combustion process and its anomalies is of paramount importance to accelerate the engine development process. In this context, the present work assesses the potential of a comprehensive quasi-dimensional model for the prediction of the combustion process, knock likelihood and cycle-by-cycle variability (CCV) specifically developed for a hydrogen-fueled ICE. The SITurb combustion model, consisting of entrainment and burn-up models, has been modified considering a tabulated approach for laminar flame speed determination. Then, it has been integrated with both a chemistry-based knock model, relying on the well-known Livengood-Wu approach, and a CCV model, in which a perturbation of the parameters included in the combustion model is induced using random variables from a Gaussian distribution. The capabilities of the developed integrated model have been validated against experimental data coming from a 0.5L PFI single-cylinder engine selected as a case study, for which a wide experimental campaign has been conducted. The developed model is capable to properly reproduce the combustion process, taking into account the CCV phenomenon, thus predicting the percentage of the knocking cycles over different spark sweeps tested for several engine operating conditions.