This study experimentally investigated the confinement effect on the boiling regime of a two-phase closed thermosyphon and heat transfer enhancement using cellulose nanofiber fluid as the working fluid. The design lengths of the condenser, adiabatic, and evaporator sections of the experiment apparatus were 400, 150, 300 mm, respectively. The filling ratios were set to 0.25, 0.5, and 0.75. The applied input power was limited to 800 W owing to the heat resistance limit of the heating block, which supplies heat to the evaporator section. By applying Confinement number of 0.245 and using de-ionized water as the working fluid, the inner diameter of the channel was set to 11 mm. The boiling regime for each level of input power was determined using the surface temperature graph of the thermocouples attached to the evaporator section. It was observed that geyser boiling occurred at a low input power; in this regime, the surface temperature was observed to have a regular long-period oscillation with a large amplitude. Subsequently, the amount of heat increased, the amplitude remained the same, and the cycle length reduced. Churn boiling regime was observed at high input power, with the surface temperature having a very small and irregular amplitude. When the input power was further increased, dry out occurred and the surface temperature soared significantly. Using cellulose nanofiber fluid as a working fluid, the critical heat flux improved by a minimum of 14.3% and the boiling heat transfer coefficient improved by up to 71.74%, compared to water. In addition, aggregation and sedimentation phenomena, which are disadvantages of existing inorganic nanofluids, were not observed after repeated experiments.