Spherical LiNi0.5Co0.3Mn0.2O2 samples with the particle size distribution between 10 and 20 μm are prepared by a hydroxide co-precipitation method and subsequent high temperature solid state calcination. Electrochemical results show that the reversible lithium storage capacities of spherical LiNi0.5Co0.3Mn0.2O2 cathode after 20 cycles are 121.5, 154.2 and 99.3 mAh g−1 in 2.0–4.3 V, 2.0–4.6 V and 2.0–4.9 V, respectively. The structural evolutions of layered materials in different working potential ranges are carefully studied by homemade in-situ X-ray diffraction techniques. It is found that the formation of hexagonal phase H3 is the main source resulting in poor electrochemical properties, where the hexagonal phase H2 to hexagonal phase H3 transition occurs at about 4.7 V in the charge process. As a result, it is expected that the suppression of hexagonal phase H3 can achieve a long-term cyclability and high reversible capacity for LiNi0.5Co0.3Mn0.2O2. Therefore, spherical LiNi0.5Co0.3Mn0.2O2 cathode shows the highest reversible lithium storage capacity of 154.2 mAh g−1 in 2.0–4.6 V after 20 cycles among all the three electrochemical working windows.