Optofluidic lasers combine the advantages of microfluidics and laser technology. Unlike traditional lasers, optofluidic lasers obtain the optical feedback from microfluidic channels with gain media (e.g., dyes) inside. Due to the small size of microfluidic channels, optofluidic lasers own the unique capabilities in terms of handling liquid of pL∼ μL volumes. Therefore, there is currently a great deal of interest in adapting optofluidic lasers for compact laser light sources and micro-total-analysis systems. Here, we use two examples to demonstrate the feasibility of using optofluidic lasers to sensitively detect DNA and protein. In the first example, the optofluidic laser is used to detect small conformational change in DNA Holliday junctions. The DNA Holliday junction has four branched double-helical arm structures, each of which is conjugated with Cy3 or Cy5 as the donor/acceptor pair. The conformational changes of the Holliday junction lead to the changes of fluorescence resonance energy transfer (FRET) between the donor and the acceptor. Using the optical feedback provided by the optofluidic laser, we are able to achieve nearly 100% wavelength switching. The FRET signal generated by the optofluidic laser is about 16 times more sensitive to DNA conformational changes than the conventional method. The second example is concerned with a fluorescent proteins laser. Green, yellow, and red optofluidic lasers based on fluorescent proteins are demonstrated, and the lasing threshold of 3 μM mCitrine is only 1 μJ/mm2. This work will potentially open a door to study protein-protein interactions via the sensitive intra-cavity laser detection method.