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The thermodynamic analysis of direct expansion solar-assisted heat pump system working with R290 as a drop-in substitute for R22 was carried out under the metrological conditions of Calicut, India. A prototype of a DXSAHP system consists of a compressor, an air-cooled condenser with evaporator-collector and thermostatic expansion valve. The experiments were carried during the winter months of 2016. The artificial intelligence technique artificial neural network integrated with genetic algorithm model was presented to predict energy and exergy performance of a system. The energy performance ratio of a system was found to be 5.75% higher and reduced heating capacity of about 6.8% when compared to R22. Similarly, the second law analysis (exergy analysis) of a total system working with R290 was found to be better when compared to baseline refrigerant. The selected alternative working fluid is a hydrocarbon and has zero ozone depletion and negligible global warming potential. Hence, R290 can be used as a drop-in substitute for R22 in DXSAHP systems.