We present a liquid refractive index (RI) sensor based on step-index multimode polymer optical fiber with a micro-hole drilled by the femtosecond laser. The experimental results show that in the RI operation range of 1.333–1.473, the sensor has a good linear loss (dB) response to the liquid RI in the micro-holes and a high sensitivity of 18 dB/RIU approximately. The experimental results are explained with the mode of the refraction loss caused by the hole–core interface and connection loss caused by the gap of the holes. The sensor has many advantages including high sensitivity and low cost.