In view of the current lack of systematic analysis and quantitative research on the load mechanism and pipeline stress evolution during the trenching and lowering of in-service subsea pipelines, OrcaFlex software was used to numerically simulate the secondary trenching and lowering of in-service subsea pipelines, and the influence of key load variations on pipeline stress under different trenching depths was quantitatively analyzed. The results indicate that temperature difference, pipeline pressure difference, and wave-current load show a linear or nonlinear positive correlation with pipeline stress; the pipeline residual tension has little effect on the pipeline stress; the existence of soil resistance can effectively reduce the stress effect of wave-current load. Under different trenching depths, the maximum variation rate of pipeline equivalent stress under the same temperature difference can reach 130 MPa/m, and the maximum stress variation rate under the same pressure difference approaches 175 MPa/m.