An in-fiber Mach–Zehnder interferometer (MZI) for high-sensitive refractive index (RI) measurement is proposed and experimentally demonstrated. The sensing head is formed by a single-mode fiber (SMF) sandwiched between two short sections of thin-core fibers (TCFs), i.e., TCF–SMF–TCF MZI configuration with a length of 9 mm. A well-defined interference pattern is obtained as the result of fiber-core mismatch and core-cladding modes interference. The selected interference dip is extremely sensitive to ambient RI, providing a stable RI response with sensitivity up to 159 nm/RIU for water-based solutions close to the RI of 1.33, making it a good candidate for bio-chemical measurements.