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To enhance heat and fluid exchange between main flow and near-wall flow in microchannels, a twisted blade-like fin with an advantage in stimulating both spanwise and normalwise secondary flow is proposed. The cross sections of the fin are low-drag airfoils in different orientations. The flow and heat transfer performances of microchannels with fins are numerically investigated at Re = 50–700. The results show that the twisted blade-like fin improves heat transfer process significantly, especially wall temperature uniformity, and reduces the flow separation region behind the fin, resulting in an obvious small pressure penalty. At small inflow (Re = 50), the best heat transfer and lowest pressure penalty are obtained in the microchannel with a single fin. When Re > 150, better heat transfer is obtained in the microchannel with three fins, and the highest comprehensive thermal performance (TP) reaches 3.58. The twisted direction of fins has a significant effect on heat transfer but less on flow drag. Due to the twisted fins, left and right walls experience an overall decline in temperature, and the temperature uniformity of top and bottom walls is improved. Compared with a smooth microchannel, the average and maximum temperature of the investigated microchannels are reduced by 48.1 K and 49.0 K at most respectively.