The pressurized water reactor (PWR) with multiple loops may have abnormal working conditions with coolant pumps out of running in some loops. In this paper, a computational fluid dynamics (CFD) numerical study of the four-loop VVER-1000 PWR pressure vessel model was presented. Numerical simulations of the thermohydrodynamic characteristics in the pressure vessel were carried out at different inlet conditions with four and three loops running, respectively. At normal stead-state condition (four-loop running), different parameters were obtained for the full fluid domain, including pressure losses across different parts, pressure, velocity and temperature distributions in the reactor pressure vessel (RPV) and mass flow distribution of the coolant at the inlet of reactor core. The obtained results for pressure losses matched with the experimental reference values of the VVER-1000 PWR at Tianwan nuclear power plant (NPP). For most fuel assemblies (FAs), the inlet flow rates presented a symmetrical distribution about the center under full-loop operation conditions, which accorded with the practical distribution. These results indicate that it is now possible to study the dynamic transition process between different asymmetric operation conditions in a multi-loop PWR using the established CFD method.