The entropy generation and natural convection in a square cavity filled with boron-water nanofluid is numerically investigated under the influence of different nanoparticle volume fractions and buoyancy forces when heated from left vertical wall and cooled from right vertical wall while horizontal walls are insulated. The results are compared with copper (Cu) and aluminum oxide (Al2O3) nanoparticles generally used in the applications. Differential equations are discretized over the SIMPLE algorithm and solved iteratively using the finite control volume method. Entropy generation contours due to heat transfer and fluid friction are presented. Local and average Bejan numbers are also investigated. The results of the study show that the entropy generation increases with the increase in Rayleigh number for all nanoparticles, and fluid friction irreversibility is more dominant in entropy generation with increasing Rayleigh number, and almost all entropy generation is caused by fluid friction in high Rayleigh numbers.