The simultaneous reduction of Green-House Gases (GHG) and criteria pollutants is the main target of current Internal Combustion Engines (ICE) development. Hydrogen (H2) fueling is one of the best options available in both regards, as it does not emit tailpipe CO2 as well as significantly abates all criteria pollutants already at engine-out level. However, optimizing hydrogen combustion in order to exploit the fuel proprieties at best is a challenging task due to the very particular properties of the fuel. In fact, H2 combustion in ICE promotes a very clean, fast and complete combustion process, with extremely low HC, CO, and PM engine-out emissions stemming only from lubricant oil. The usage of lean-boosted and EGR-diluted combustion strategies can significantly contribute to raise the brake thermal efficiency and lower the NOx emission to extremely low levels. To this end, the Authors tested a 0.5 L single cylinder engine featuring an optimized PFI layout and dedicated piston bowl profile for a retrofitted Diesel operating as H2 monofuel, in SI mode. In this paper, the authors discuss the effect of the main engine parameters, extensively investigated by means of Design of Experiments (DoE) techniques, as well as the effect of dilution and EGR to promote clean and efficient hydrogen combustion, in order to recommend the most effective practices.