The focus of immersed tunnel research has primarily revolved around settlement monitoring or prediction. However, there has been a lack of discussion regarding the time-dependent effects on settlement prediction, which could lead to obvious misjudgments in subsequent maintenance work. This paper addresses this issue by applying the physics-informed machine learning (PIML) algorithm to conduct an inverse analysis of the foundation modulus of the Hong Kong-Zhuhai-Macau Bridge (HZMB) tunnel, thereby identifying its variation tendency with time. The proposed time-dependent expression of foundation modulus demonstrates that the time-dependent effect is related to both post-construction settlement and the accumulation of back silting, which is significant and could persist throughout the entire service life of the HZMB tunnel. In further studies on settlement prediction for the HZMB tunnel, the results show that errors in prediction can exceed 30 mm at certain monitoring points. This error can be mitigated by considering the time-dependent effect, thereby significantly enhancing the reliability of predictions.