A numerical model is developed to analyze the flow and heat transfer in nanofluid-cooled microchannel heat sink (MCHS). In the MCHS model, temperature-dependent thermophysical properties are taken into account due to large temperature differences in the MCHS and strong temperature-dependent characteristics of nanofluids, the model is validated by experimental data with good agreement. The simplified conjugate-gradient method is coupled with MCHS model as optimization tool. Three geometric parameters, including channel number, channel aspect ratio, and width ratio of channel to pitch, are simultaneously optimized at fixed inlet volume flow rate, fixed pumping power, and fixed pressure drop as constraint condition, respectively. The optimal designs of MCHS are obtained for various constraint conditions and the effects of inlet volume flow rate, pumping power, and pressure drop on the optimal geometric parameters are discussed. (C) 2012 Elsevier Ltd. All rights reserved.