We propose an effective method for biomolecular detection based on an external referencing optofluidic microbubble resonator system (EROMBRS), which possesses good long-term stability and low noise. In this study, EROMBRSs were used for nonspecific detection of bovine serum albumin (BSA) molecules and specific detection of D-biotin molecules. Ultra-low practical detection limits of 1 fg/mL for nonspecific and specific biomolecular detection were achieved.