Due to the rapid development in micro manufacturing and 3D printing technology, the complex shape of microchannel heat sink (MCHS) can be realized, instead of just the traditional rectangular channels. It is recognized that twisted square channels which are similar to a kind of internal thread channel have favorable effects on heat transfer because of its enhancement of turbulence intensity. In this work, a geometry of twisted tube is applied to the microchannel and the thermal and hydrodynamic performance of twisted square microchannels with jet impingement are investigated. The arrangement of the jet channels is the research focus and one-jet and multi-jet microchannel heat sinks are compared by discussing the temperature profile, pressure drop and heat transfer characteristics. By applying the twisted geometry to the microchannel, the Nusselt number can be increased by 16.48% with little increase in pressure drop. However, with the increase in torsion angle of the twisted microchannel (from 90° to 720°), the thermal performance changes little for the limited effect on the temperature uniformity of the cross section. Integration of jet impingement further improves the thermal-hydrodynamic performance of MCHS. Specifically, the thermal resistance of MCHS was reduced by 41% at most. Finally, by comparing the comprehensive performance of the cases with varied jet arrangement, it is concluded that jets distributed at the cross section with the torsion angle of 45°, 135°, and 225° can induce better performance. The present investigation combines the twisted geometry and jet impingement into microchannel, quantitatively characterizes the performance of MCHS and gives the guidance for the jet arrangement design.