A Mach–Zehnder interferometer (MZI) composed of electro-optical polymer/silicon hybrid slot waveguides is reported. The device is designed to be asymmetrical so that the modulator is in a linear workspace when no electric field is applied to the initial operating state. We rely on the fast and strong nonlinearities of CLD-1/PMMA that infiltrates silicon rather than on the slower free-carrier effect in silicon. The modulated arm waveguides are designed in the shape of silicon/polymer hybrid slot waveguides to increase the interaction of the polymer material with the light field. The results show that the loss of the proposed MZI is 3.51 dB with a core size of 420μm × 160μm, and the half-wave voltage of the MZI is 2.1 V at 1550 nm, which provides the possibility of application in measuring small signals from an electrocardiogram with the optical principle.