Although progress has been made on the influence of soil liquefaction and soil-structure interaction (SSI) on the structural response, studies combining both phenomena are very limited, if not existent. To bridge this gap, the objective of this study is to implement a numerical investigation of the influence of both liquefaction and SSI on the seismic performance of typical reinforced concrete (RC), low-code (LC), moment resisting frame (MRF) port buildings. In particular, the following numerical modelling approaches are applied: i) a fixed-base structural model subjected to free-field motion that neglects liquefaction and SSI; ii) a fixed-base structural model subjected to free-field motion that considers liquefaction; iii) a SSI system that neglects liquefaction; iv) a SSI system that considers liquefaction. Finally, comparative results of the above numerical approaches are presented, which show the significant role of liquefaction and SSI in altering the expected structural performance of port buildings.