Electrochemical tip-enhanced Raman spectroscopy (EC-TERS) appears as a promising in situ nanospectroscopic tool for characterization and understanding of the electrochemical interfacial processes at the nanometer scale and molecular level. However, the wide application of EC-TERS is hampered by its low sensitivity as a result of the optical path distortion due to the refractive index mismatch of the multilayer media (air, glass, and electrolyte). Here, we propose a new side-illumination EC-TERS setup by coupling a water immersion objective with a high numerical aperture to a scanning tunneling microscope scanning head customized with a large open space and a compact spectroelectrochemical cell. It not only effectively eliminates the optical distortion but also increases the sensitivity remarkably, which allows sensitive monitoring of the electrochemical redox processes of anthraquinone molecules. More importantly, EC-TERS is able to independently control the tip position and laser illumination position. By utilizing this feature, we reveal that the irreversible reduction reaction of anthraquinone observed in EC-TERS is induced by the synergistic effect of the negative potential and laser illumination rather than the localized surface plasmon. The highly improved sensitivity and the flexibility to control the tip and laser illumination position on the nanometer scale endows EC-TERS as an important tool for the fundamental understanding of the photo- or plasmon electrochemistry and the interfacial structure-activity relationship of important electrochemical systems.