With the booming of nanotechnology, surface plasmon resonance (SPR) technology has become one of the most active research hotspots in optical sensing. In this work, a square-lattice photonic crystal fiber (PCF) sensor based-SPR with indium tin oxide (ITO) coating is investigated to detect analytes with large refractive indexes (RIs) varying from 1.380 to 1.405. To confirm the dependence of sensing characteristics on the geometrical parameters, the finite element method (FEM) is applied to modeling and numerical simulation. The big air holes in cladding cause a birefringence effect, which is stronger with y-polarization mode. In this way, the maximum and average spectral sensitivity of 60,000 and 18,400 nm/RIU can be achieved with resolution in 10−6 order. Furthermore, this sensor which provides a high-sensitivity detection in large analyte RIs with near-infrared region (1500–2800 nm) shows excellent figure of merit (FOM), signal-to-noise ratio (SNR) and detection limit (DL). There will be more extensive space and prospect for progression in biochemical safety with DNA hybridization, blood glucose analysis and organic chemical samples detection involved.