This paper focused on the fatigue crack growth behavior of TC4-DT titanium alloy with different lamellar microstructures. Heat treatments were performed in order to prepare different microstructures with α lamella width and colony size. The results show that on the premise to guarantee adequate mechanical properties, the microstructures formed through air cooling from the β-phase field present better ability to resist fatigue crack propagation. This is attributed to the existing of bigger plastic deformation field in crack tip. It is also found that wide α lamellae and coarse α colony are beneficial to improve fracture toughness and resistance to fatigue crack propagation