The objective of this paper is to investigate the influence of nanoparticles on the heat transfer characteristics of refrigerant-based nanofluid flow boiling inside a horizontal smooth tube, and to present a correlation for predicting heat transfer performance of refrigerant-based nanofluid. For the convenience of preparing refrigerant-based nanofluid, R113 refrigerant and CuO nanoparticles were used. Experimental conditions include an evaporation pressure of 78.25 kPa, mass fluxes from 100 to 200 kg m −2 s −1, heat fluxes from 3.08 to 6.16 kW m −2, inlet vapor qualities from 0.2 to 0.7, and mass fractions of nanoparticles from 0 to 0.5 wt%. The experimental results show that the heat transfer coefficient of refrigerant-based nanofluid is larger than that of pure refrigerant, and the maximum enhancement of heat transfer coefficient is 29.7%. A heat transfer correlation for refrigerant-based nanofluid is proposed, and the predictions agree with 93% of the experimental data within the deviation of ±20%.