Ti-62421S (Ti–6Al–2Sn–4Zr–2Nb–1Mo–0.2Si) is a novel short-time using high-temperature titanium alloy. The effects of annealing on microstructure and tensile properties of Ti-62421S alloy plate were studied through optical microscopy (OM), electron probe microanalysis (EPMA), transmission electron microscopy (TEM), and tensile tests. The results show that, with annealing tem-perature increasing, the volume fraction of primary α (αp)-phase decreases while that of transformed β (βt)-structure and secondary α (αs)-phase increases. The room-tempera-ture strength and plasticity are insensitive to annealing temperature. However, with annealing temperature increasing, the tensile strength decreases at 550 ℃, while increases at 600 and 650 ℃ instead. It is suggested that, at 550 ℃, the strengthening mechanism is mainly boundary strengthening and the biggest contributor is αp-phase by providing αp/β-boundary area. Above 600 ℃, the strengthening mechanism is grain strengthening, where αs-phase strengthens the β-phase.