In this study, the analysis of heat transfer characteristics of VVER-1000 nuclear reactor by using hybrid nanofluids as a coolants in subchannels in hot fuel assembly have been performed. Firstly, the criticality (keff) and fuel assembly power distributions of the VVER-1000 reactor by using Monte Carlo particle transport (MCNP) code to determine of the heat transfer characteristics with COBRA IV PC code have been examined. Secondly, the axial coolant temperature distributions and Departure from Nucleate Boiling Ratio (DNBR) values in hottest channel for Cu, CuO and TiO2 nanoparticles of the different volume fractions (0.05%, 0.01% and 0.1%) mixed with 0.1 vol % Al2O3 hybrid nanofluids have been analyzed. The obtained results by using hybrid nanofluids have been compared with the pure water results. The keff decreases with the increase of volumetric fractions of hybrid nanoparticles Cu, CuO and TiO2 mixed with 0.1% Al2O3 in the coolant. The maximum temperature has been reached by the püre water coolant at the end of the channel as 612.68 K whereas, the highest temperature change has been obtained in the case of 0.1% Al2O3 + 0.1% TiO2 as 617.35 K when evaluated among nanoparticle themselves. The results of analysis show that the heat transfer enhances with increasing hybrid nanoparticles volume fractions in the subchannel geometry. Also, the obtained minimum DNBR values using hybrid nanofluid haven't been exceed the safe operational limits; therefore the reactor operation would be safer.