Based on the calculated results of the simplified model of deep-water semi-submerged drilling unit, the model of deep-water semi-submerged drilling unit is built by reasonably simplifying. The large vertical cylinder (MacCamy-Fuchs) formula is modified according to this model, then the modified formula is utilized to obtain the wave load spectrum which acts on the columns of the semi-submerged drilling unit. By using ANSYS software, a spectrum analysis process is established to calculate the stochastic response spectrum of the model that is subjected to the wave load spectrum which has been calculated. Then the power spectral density of stochastic response of the key nodes can be obtained. Based on the Miner model and the first excursion failure criterion, the fatigue life reliability of the key nodes is calculated. © 2011 Shanghai Jiaotong University and Springer-Verlag Berlin Heidelberg.