Research has been undertaken on heat pipe evacuated tube solar collector (HP-ETSC) for hot water applications, which is common in most Middle East regions. The enhancement in thermal performance by using various types of acetone based nanofluids has been explored. This work includes two experimental parts of the gravity-assisted heat pipe (GAHP) installed in evacuated tube solar collector system. The first part is designed to reach the optimal performance conditions for HP-ETSC which is charged with acetone as a working fluid inside the GAHP. Various values of filling ratios (40, 50, 60, 70 and 80%) and tilt angles (30 degrees, 45 degrees and 60 degrees) are considered. The results show that there is an optimal performance at filling ratio equal to 70% and inclination angle equal to 45 degrees when compared with other values during the course of study. This indicates that the importance of fully integrating design process right from the outset of the system design if GAHP is to be installed into an ETSC system to give the maximum possible solar energy benefits of efficient hot water solar collector designs. The main objective of the second experimental investigation is analyzing the impact of the two types of nanofluid (Al2O3 and CuO/acetone-based) on the thermal performance of the HP-ETSC. These two nanofluids are used as working fluid inside the GAHP and two concentration values (0.25% and 0.5% vol.) at the optimal conditions from the first experimental part. On the basis of the present study, it is recommended that HP-ETSC systems should be charged with nanofluids for thermal performance enhancement (20-54%) and efficiency (15-38%).