Considering the special wellbore configuration and operating environment of deep-water drilling, a comprehensive model for circulating pressure loss of deep-water drilling is established. Based on fluid mechanics theory and heat transfer theory, wellbore temperature and pressure of riser section are calculated and a coupling approach is proposed. Comprehensive factors that affect circulating pressure loss of deep-water drilling are considered in this study. These factors are mud properties, flow regime, drill pipe rotation, drill pipe eccentricity, cuttings bed, tool joints, BHA (Bottom Hole Assembly), drill bit and surface pipeline. The model is applied to Liwan gas field of China. The results show that the data calculated by this model match the field data very well and the model can provide references for designing deep-water drilling hydraulic parameters.