High power consumption of air conditioners and refrigerators is a big problem. Accordingly, many directions for achieving energy efficient air conditioning and refrigeration systems with environmentally friendly refrigerants need to be explored to face the depletion energy resources. Vapor compression refrigeration system is one of the many refrigeration cycles and is the most widespread method for refrigeration, air conditioning and heat pump. On the other hand, the rapid progress in technology of nanoparticles have led to combine a novel generation of heat transfer fluids called nanofluids in which addition of nanoparticles to base fluids changes their heat transfer characteristics. In the present study, the effect of using CuO-POE and Al2O3-POE nanolubricant on the flow boiling heat transfer coefficient (HTC) of R404a refrigerant is experimentally investigated. The experiments have been carried out at different nanoparticles concentration ranged from 0.20 vol.% to 0.70 vol.% for Al2O3 and from 0.05 vol.% to 0.25 vol.% for CuO, with nanoparticles size of 50-60 nm and at heat flux ranged from 10 to 12 kW/m2. The results showe enhancement in flow boiling heat transfer coefficient (HTC) of R404a with using Al2O3-POE and CuO-POE nanolubricant. It is found that flow boiling HTC increases with increasing the heat flux for the tested range. Also, it is noticed that the flow boiling HTC increases with increasing the nanoparticles concentration in POE oil up to 0.60% by volume for Al2O3 and 0.2 vol.% for CuO then deteriorates.