Designing a hybrid supercapacitor, composed of Li4Ti5O12(LTO)/activated carbon (AC), is one of promising routes to enhance the energy density of supercapacitors (SCs) using symmetrical AC electrodes. At high-voltage operations (>3.0 V), however, the failure mode or gas generation is critical for the system, which is greatly dependent on the type of electrolyte. In this study, we investigated the voltage dependence of the interfacial phenomena of LTO/1 M lithium tetrafluoroborate (LiBF4) in propylene carbonate (PC)/AC. The results reveal that the interface between the negative LTO electrode and the electrolyte becomes unstable at cell voltages above 3.0 V, corresponding to potentials above 4.5 V vs. Li/Li+ for the AC positive electrode. The destabilization of the LTO/electrolyte interface appears to be initiated by an irreversible reaction occurring at the AC positive electrode, accompanied by a release of absorbed H2O. This hypothesis is further confirmed by replacing PC with a hydrolysis-resistant solvent, ethyl isopropyl sulfone (EiPS); the EiPS-based electrolyte successfully realizes a high-voltage operation at 3.3 V without LTO degradation, regardless of the oxidative reaction at the AC positive electrode, with a 95% capacity retention after 1000 cycles.