Thermodynamic vent system (TVS) is deemed as an efficient pressure control technique for long-term on-orbit storage of cryogenic propellants through fluid mixing and a combination of throttling and heat exchanging before venting. To conduct further study on the performance of tank pressure control by TVS under non-uniform heat flux, the effect of non-uniform heat flux (vapor heating only, liquid heating only and one side wall heating for both vapor and liquid) on self-pressurization characteristics and mass loss has been investigated experimentally on a TVS simulator, which works at room temperature and with R141b as the working fluid. The tank pressure rising rate, TVS operation performance, and vent mass loss of different heating condition were compared in detail. The results showed that under the condition of vapor heating mode, the rising rate of the tank pressure is the fastest, the TVS operation frequency and vent mass loss are the highest. However, under the condition of liquid heating mode, the rising rate of the tank pressure is the slowest, the TVS operation frequency and vent mass loss are the lowest, which decreased by 42%, 29% and 33%, respectively, compared with the liquid heating mode. Considering the overall effect by the pressure rising rate, the thermal stratification of the fluid and the vent mass loss, the internal wall surface of the tank is better to have hydrophilic treatment or to integrate capillary structures to avoid direct heating of the ullage in micro-gravity environment.