Low cycle fatigue behavior of TC4 ELI titanium alloy with bimodal and lamellar microstructure had been investigated by analyzation of strain-cycles curve with different stress amplitudes. Results indicated that the volume fraction of equiaxed α phase is about ~ 26.6% for the bimodal microstructure, the average grain size is approximate 7.8 μm. At the same time, the thickness of α phase layer is about 0.5 ~ 2.0 μm for lamellar microstructure. Cyclic softening phenomenon was observed for all the samples of TC4 ELI alloys with different microstructure at the maximum stress. Sample with bimodal microstructure exhibited higher low cycle fatigue life, which could be attributed to the shorter effective slip path than the one with lamellar microstructure. More than that, the presence of equiaxed α-phase with high dislocation density also could hinder the initiation and propagation of fatigue cracks for the bimodal microstructure. Fracture morphology shown flat and smooth for the sample with bimodal microstructure, however, some geometric facets associated with the original coarse-grained β were found for the sample with lamellar microstructure.