High-Ni layered oxides are one class of the most promising cathodes for Lithium ion batteries (LIBs) due to the high capacity and low cost. Accompanying with the high Ni content, Li/O loss from the layered structure, as well as the relevant structural evolution, have been extensively considered as a general origin for various detrimental phenomena, such as cationic disordering during high-temperature solid-state synthesis, chemical weathering at the surface during storage, and the capacity fading at high upper voltages (> 4.3 V) during electrochemical tests. Herein, multiple macroscopic/microscopic characterization techniques, including in-situ transmission electron microscopy (TEM), ex-situ X-ray diffraction (XRD), and X-ray photoelectron spectra (XPS), are combined to comprehensively investigate the thermal-induced local structural evolution vs Li/O loss in a representative binary high-Ni layered oxide LiNi0.9Co0.1O2. The heterogenous Li/O loss kinetics in the bulk and at the surface are simultaneously tracked based on a rational structural model, revealing a quantitative relationship between Li/O loss and the phase transformation. The local structural evolution within single primary particles monitored by in-situ TEM further uncovers that, Li/O loss at the particle surface is accelerated via the large Li+ diffusivity at high temperatures, finally leads to a phase transformation process from the bulk to the surface, in which a peculiar “anti-core-shell” structure within single primary particles is observed. The quantitative analysis combined with the direct observation not only demonstrate a feasible route to investigate the Li/O loss kinetics, but also provide valuable insights into the performance improvement of high-Ni layered oxides from the aspect of Li/O loss.