Bilirubin is an important biomarker in the diagnosis and prognosis of patients with liver disorders. Herein, we report a simple, rapid, sensitive and selective quantitative determination of bilirubin using molybdenum disulfide quantum dots (MoS QDs) as a probe. The MoS QDs were synthesized through a hydrothermal route by using sodium molybdate and cysteine as the starting materials. The obtained MoS QDs exhibits strong luminescence property and excellent stability. The HR-TEM image shows that the size of the prepared MoS QDs was 2.4 nm with a spherical morphology. The MoS QDs emit intense blue photoluminescence (with excitation/emission peaks at 310/392 nm) under UV light and the fluorescence of MoS QDs was drastically quenched by the addition of bilirubin. The Förster resonance energy transfer (FRET) and inner filter effect (IFE) between MoS QDs and bilirubin resulted in the fluorescence quenching of MoS QDs. The present method demonstrated high sensitivity towards bilirubin with the limit of detection (LOD) of 2.1 nM (S/N = 3). The MoS QDs probe showed remarkable selectivity to bilirubin over other possible interferences. Moreover, the present fluorophore was successfully utilized for the detection of bilirubin in human serum and urine samples. QDs based fluorescence probe for the recognition of bilirubin is reported for the first time.