This study presents the effect of nanoparticle mass concentration and heat input based on the total thermal resistance ( R _th ) of loop heat pipe (LHP), employed for PC-CPU cooling. In this study, silica nanoparticles (SiO₂) in water with particle mass concentration ranged from 0% (pure water) to 3% is considered as the working fluid within the LHP. The experimental design and optimization is accomplished by the design of experimental tool, Response Surface Methodology (RSM). The results show that the nanoparticle mass concentration and the heat input have significant effect on the R _th of LHP. For a given heat input, the R _th is found to decrease with the increase of the nanoparticle mass concentration up to 0.5% and increased thereafter. It is also found that the R _th is decreased when the heat input is increased from 20 W to 60 W. The results are optimized with the objective of minimizing the R _th , using Design-Expert software, and the optimized nanoparticle mass concentration and heat input are 0.48% and 59.97 W, respectively, the minimum R _th being 2.66 (ºC/W). The existence of an optimum nanoparticle mass concentration and heat input are the predominant factors for the improvement in the thermal performance of nanofluid-charged LHP.