In this paper a detailed procedure to study the mooring line strength reliability of a semi-submersible platform is presented. A fully coupled analysis is conducted to calculate the mooring line tension of a deep water semi-submersible floating system operated in the 100-year wave condition in South China Sea. The Average Conditional Exceedance Rate (ACER) method is applied to predict the 3-hour extreme mooring line tension based on 10 and 20 minutes fully coupled dynamic simulation and the results are validated by the global maximum method. A Kriging metamodel is trained to predict the 3-hour mooring line extreme tension taking into account the effect of random hydrodynamic drag coefficients. The hydrodynamic sampling points are generated by Latin Hypercube Sampling technique. A reliability analysis is carried out by Monte Carlo simulation considering the random hydrodynamic drag coefficients and mooring line breaking strength.