The nematic-isotropic (NI) phase transition of 4-cyano-4'-pentylbiphenyl was simulated using the generalized replica-exchange method (gREM) based on molecular dynamics simulations. The effective temperature is introduced in the gREM, allowing for the enhanced sampling of configurations in the unstable region, which is intrinsic to the first-order phase transition. The sampling performance was analyzed with different system sizes and compared with that of the temperature replica-exchange method (tREM). It was observed that gREM is capable of sampling configurations at sufficient replica-exchange acceptance ratios even around the NI transition temperature. A bimodal distribution of the order parameter at the transition region was found, which is in agreement with the mean-field theory. In contrast, tREM is ineffective around the transition temperature owing to the potential energy gap between the nematic and isotropic phases.