The paper presented topology optimization of 2D and 3D Nanofluid-Cooled Heat Sink (NCHS). The flow and heat transfer problem in the NCHS was treated as a single-phase nanofluid based convective heat transfer model. The temperature-dependent fluid properties were taken into account in the model due to the strong temperature-dependent features of nanofluids. An average temperature minimum problem was studied subject to the fluid area and energy dissipation con-straints by using the density method. In the method, the design variable is updated according to the gradient information obtained by an adjoint based sensitivity analysis process. The effects of the energy dissipation constraint, temperature-dependent fluid properties and nanofluid character-istics on optimal configurations of NCHS were numerically investigated with following conclusions. Firstly, branched flow channels in the optimal configuration increased with the rise of the allowed energy dissipation. Secondly, temperature-dependent fluid properties were significant for obtaining the appropriate optimal results with best cooling performance. Thirdly, heat transfer performances of optimal configurations were enhanced by reducing the nanoparticle diameter or increasing the nanoparticle volume fraction. Fourthly, the optimal configuration for nanofluid had better cooling performance than that for its base fluid.