The exploitations of deep-water wells often use directional well drilling to reach the target layer. Affected by special environments in deep water, the prediction of pressure loss of cement slurry is particularly important. This paper presents a prediction model of pressure loss suitable for deep-water directional wells. This model takes the complex interaction between the temperature, pressure and hydration kinetics of cement slurry into account. Based on the initial and boundary conditions, the finite difference method is used to discretize and calculate the model to ensure the stability and convergence of the result calculated by this model. Finally, the calculation equation of the model is used to predict the transient temperature and pressure loss of Wells X1 and X2, and a comparison is made between the predicted value and the monitoring data. The comparison results show that the maximum error between the temperature and pressure predicted by the model and the field measured value is within 6%. Thus, this model is of high accuracy and can meet the needs of site construction. It is concluded that this result can provide reliable theoretical guidance for temperature and pressure prediction, as well as the anti-channeling design of HTHP directional wells.