An in situ experimental technique was developed for detecting structure changes at the electrode/electrolyte interface of lithium cell using synchrotron X-ray reflectometry and two-dimensional model electrodes with a restricted lattice plane. The electrode was constructed with an epitaxial film of LiNi0.8Co0.2O2 synthesized by the pulsed laser deposition method. The orientation of the epitaxial film depends on the substrate plane; the 2D layer of LiNi0.8Co0.2O2 is parallel to the SrTiO3 (111) substrate ( ( 0 0 3 ) LiC o 0.2 N i 0.8 O 2 / / ( 1 1 1 ) SrTi O 3 ) , while the 2D layer is perpendicular to the SrTiO3 (110) substrate ( ( 1 1 0 ) LiC o 0.2 N i 0.8 O 2 / / ( 1 1 0 ) SrTi O 3 ) . These films provided an ideal reaction field suitable for detecting structure changes at the electrode/electrolyte interface during the electrochemical reaction. The X-ray reflectometry indicated a formation of a thin-film layer at the LiNi0.8Co0.2O2 (110)/electrolyte interface during the first charge–discharge cycle, while the LiNi0.8Co0.2O2 (003) surface showed an increase in the surface roughness without forming the surface thin-film layer. The reaction mechanism at the electrode/electrolyte interface is discussed based on our new experimental technique for lithium batteries.