This study proposes an empirical formulation to assess the ultimate strength of side shells on passenger ships subjected to combined effects of axial compression and shear loads. The deteriorating effects of large openings and strengthening effects of stiffener reinforcements were considered in the proposed formulation for a wider range of applications. To verify accuracy of the empirical formula, an experimental test was first conducted to inspect the collapse behaviour and influential parameters of the side shell. More than 5000 side-shell scenarios were subsequently adopted as the input dataset based on the experimentally validated nonlinear finite element method. A simplified polynomial shape was proposed for the empirical formula by comparing various generation sets of the four-parameter-based formulations. A reliable solution to the proposed empirical formula was obtained with respect to a high determination coefficient compared to the numerical results. The developed empirical formula can be considered as applicable and beneficial for practical structural design work of side shells with large openings in modern passenger ships.