Optical fiber sensors are capable of converting the external environmental information they perceive into optical signal output in a specific pattern, which can provide the measured information while detecting and feeding back real-time changes in the external environment. When the environment changes, such as alterations in Refractive Index (RI), pH, temperature, humidity, biomolecules, etc, some characteristics of the optical wave signal inside the optical fiber sensing unit will also change. The fiber RI sensor based on the hybrid optical waveguide utilizes the cascading of different fiber waveguides to excite the intermodal interference effect, and has the advantages of small size and high sensitivity. However, there is still room for improvement in RI sensitivity, and one effective approach is to employ fiber micro-nano processing techniques to boost the evanescent field intensity, thus enhancing the RI sensitivity. Due to the merits of a simple manufacturing process, low cost, and high stability, this kind of sensor can be applied in a variety of complex industrial environments. This paper proposes and investigates a high-sensitivity RI sensor based on a Single Mode Fiber-Photonic Crystal Fiber-Single Mode Fiber (SMF-PCF-SMF) hybrid optical waveguide. This structure is axially fusion-spliced in sequence by SMF, PCF, and SMF, the length of the collapse area can be kept within the range of 150~160 μm through controlling the welding parameters, and enables the mutual excitation and coupling of the core mode and the cladding mode in the two-side collapse area. Theoretically analyze the sensing principle, and utilize the beam propagation algorithm to simulate the light-field energy distribution and exchange process, thereby obtaining its output spectrum. The simulation results indicate that when the light field enters the PCF from SMF, the high-order mode in the PCF is excited as it passes through the first collapsed area, with the energy being reduced and energy exchange taking place. After traveling a certain distance within the PCF, it reaches the second collapsed area. At the junction with the other SMF, the light converges and enters SMF for transmission, and the light energy is enhanced. Furthermore, when the PCF section is tapered, compressing the cladding thickness of the PCF section can increase the sensitivity of the structure to the change in the external RI, enhance the spectral redshift of the SMF-PCF-SMF hybrid optical waveguide structure, and raise its RI sensing sensitivity. The methods for achieving the enhancement of the evanescent field are investigated. Based on three micro-nano processing techniques, namely the fiber cladding polishing method, the hydrofluoric (HF) acid fiber cladding etching method and the fused biconical taper method, the device preparation is accomplished. The interference spectral characteristics of the SMF-PCF-SMF hybrid optical waveguide structure obtained through three processing techniques are experimentally tested and compared. Moreover, a microfluidic fixture (manufactured by using polytetrafluoroethylene material in combination with precision micromachining methods) is utilized to package the sensor. The RI sensing characteristics of liquid samples in SMF-PCF-SMF structures with three polishing depths, in SMF-PCF-SMF structures with HF acid etching, and in SMF-PCF-SMF structures where the cladding thickness of the PCF in the middle section is compressed by the fused biconical taper method are respectively tested and compared. The experimental results demonstrate that all three micro-nano processing methods have enhanced the linearity of RI sensing. Furthermore, by compressing the cladding thickness of the PCF in the middle section of the SMF-PCF-SMF structure through the fused biconical taper method, the obtained RI sensitivity of the liquid sample is the highest, reaching 1 405.36 nm/RIU, which is approximately 24 times higher. This RI sensor is characterized by its small size, easy integration and high sensitivity, and it has significant application value in the fields of RI sensing, industrial production, etc.