A multimode plastic optical fiber with a sidehole fabricated by precision mechanical drilling technology is presented for refractive index (RI) sensing. A higher sensitivity of 1862.1 µW/RIU, when center wavelength of optical source is 652 nm and launched power is 1 mW, is obtained in a larger hole diameter of 350 µm, indicating that the larger hole diameter can increase the sensitivity of the sensor. Ray-optics method and finite-difference time-domain method are both utilized to theoretically evaluate the characteristics of the structure for RI testing, which is well in agreement with the experimental results. Energy field distribution is analyzed to explain the sensing mechanism of the structure, which demonstrates that the divergent effect of the side-hole like a negative lens is the key to sensing. Due to the advantages of relatively easy fabrication, low cost, and capable of continuous measurement, this side-holebased fiber sensing structure is attractive for RI monitoring in chemical, biological, and biochemical sensing region.Index Terms-Plastic optical fiber, refractive index sensing, side-hole structure.