The opening of segment joints is considered critical for the stability analysis of a shield tunnel lining. In order to prevent tunnel disasters, an integrated framework was developed in this study based on the laboratory experiment, real-time monitoring, and statistic theory. As a case study, this presented method was employed in a typical underwater shield tunnel to prevent leakage disasters. The water pressure experiment was used to analyze the importance of joint openings for the tunnel waterproofing. Then, an automatic structural health monitoring system was installed in the study site to have real-time monitoring of segment joint opening and the variation of external load applied to the structure. Based on the monitoring data, a multiple linear regression model was developed to explain the response of joint opening to water pressure and temperature at the important positions of arch crown, spandrel, and hance of the tunnel. The multiple linear regression results were verified to be in agreement with those of the numerical simulation; they denote that (1) joint opening decreased with the rise in temperature, but increased with the rise in water pressure at arch crown and hance, and (2) the segment joint opening decreased with the rise in water pressure at spandrel. As a potential application, the developed model was applied to predict future behaviors of structure, which is vital to prevent disasters and provides a reference to underwater constructions.