Abstract: During deepwater drilling operations, the drilling string extending from a platform to the bottom hole will collide and rub with the riser or wellbore at multiple points at different depths, presenting the characteristics of nonlinear contact. In order to accurately understand the nonlinear dynamic characteristics of deepwater drilling string systems, we proposed a dynamic model that based on the structure of pipe-in-pipe. The dynamic response simulation was conducted by using Abaqus finite element software, and then the simulation results were imported to Isight optimization software to carry out the multi-objective optimization design based on reliability analysis to determine the combination of design parameters that meet the requirement of engineering feasibility and safety reliability. The study suggests that the overall deformation of the string system from the proposed pipe-in-pipe model is smaller when compared with a model that only considers the riser, indicating that the overall offset of deepwater drilling string system is restrained by the interaction between the inner and outer strings. In addition, the proposed multi-objective optimization design method based on reliability analysis can effectively avoid the failed optimization design caused by parameter fluctuations in the vicinity of the constraint boundary.