Nitrite ion (NO2-) is a common contaminant that can significantly threaten human health and the environment. In this study, we demonstrate a chemical sensing platform to monitor the nitrite concentration using a fiber optofluidic laser (FOFL). An optical fiber, integrated into a microchannel, is used both as an optical micro-cavity and the sensing element. Rhodamine 6 G (Rh6G) in an aqueous micellar solution is used as the laser gain medium. The light intensity change of the lasing spectra is employed as an indicator for the NO2- ion concentration sensing. The lasing properties under different NO2- ion concentrations are experimentally and theoretically investigated to examine the sensing performance of the FOFL. The results show that the limit detection of the FOFL sensor is 0.54 µM, which is 2-order-of-magnitude lower than fluorescence measurement. The sensing mechanism of Rh6G for NO2- detection is studied by using density functional theory (DFT). The calculation results indicate that nitrite influences the electronic distribution of Rh6G based on the heavy atom effect, which leads to the fluorescence quenching of Rh6G in the excited state. In addition, the detection system exhibits favorable selectivity for NO2- ions.