In this study, entropy generation caused by heat transfer and friction of forced convection flow in a semicircular cross-sectioned microchannel with TiO2/water nanofluid was numerically analyzed. The volume concentrations of the nanofluid were taken 1.0%, 2.0%, 3.0%, and 4.0%. Local and total entropy generation due to the heat transfer and friction were calculated for the microchannel. A three-dimensional analysis was simulated under steady-state laminar flow conditions with Reynolds number varying from 100 to 1000. The results of the simulation were obtained using the CFD code. The flow was considered as hydrodynamically fully developed under thermally developing conditions. A uniform heat flux boundary condition was applied at the bottom surface of the microchannel. According to the results of the numerical study, the effect of the nanofluid volume concentration and fluid velocity on entropy generation was evaluated. The findings show that the total and friction values of entropy generation increase with increasing flow velocity, while heat transfer entropy generation values decrease since nanofluids improve the heat transfer capability. Also, the results indicate that an increase in the volume concentration of the nanofluid causes friction entropy generation enhancement while heat transfer entropy generation decreases in all cases.