There are multiple factors influencing the foundation settlement of deep-sea immersed tunnels, and excessive settlement will directly affect the safety of the tunnel. Therefore, it is necessary to analyze the sensitivity of various construction deviations affecting the foundation settlement. Taking the foundation of the Hong Kong-Zhuhai-Macao immersed tunnel as the research object, the centrifugal model test supplemented by the finite element verification method was used to reveal the variation characteristics of the backfill recompression amount and the foundation stiffness, according to which the single factor sensitivity of the longitudinal settlement of the natural foundation of the Hong Kong-Zhuhai-Macao immersed tunnel was determined. The results show that the most influential factor of the settlement of immersed tunnel is the overbreak and underbreak deviation of foundation trench, and the least influential factor is the unilateral width deviation of foundation trench. When the overbreak and underbreak excavation deviation of foundation trench is present, its influencing degree on the foundation stiffness under the combined working condition can reach 50%, and when it reaches the limit value, its influencing degree on the settlement characteristics of the immersed tunnel is no less than 20%, no matter what other sensitive factors are combined. Based on the analyses of multiple combinations of sensitivity factors, it is found that the most unfavorable working condition distribution in the longitudinal section is the constant extreme value on both sides of the section, i.e., the nonlinear variation distribution. The research results can provide some reference for other similar projects.