Fluorescence-based single-molecule detection has been widely investigated and applied in biosensing and bioimaging due to its ultrahigh sensitivity and specificity. However, bulky and expensive commercial fluorescence microscopes are usually required. The Stokes shift property of most commonly used fluorophores requires optical sets such as dichroic mirrors and specific filters in the optical pathway before a photodetector to eliminate excitation and scattering lights from the fluorescence signals. The fluorescence signal collected by an objective is further unavoidably attenuated, and the optical resolution is diffraction-limited. Herein, a proof of concept of a lab-on-a-chip compatible molecular sensor is shown by integrating upconversion nanoparticles (UCNPs) and amorphous hydrogen-doped InGaZnO (InGaZnO:H) thin-film phototransistor (IGZO:H TFTs) aiming to alleviate those issues. Upon illumination with a 980 nm infrared light, the phototransistor shows no photocurrent without UCNPs but yields a high photocurrent with UV-visible fluorescent light emitted from the UCNPs. The molecular detection is enabled by further involving the Förster resonance energy transfer (FRET) mechanism, with the UCNPs as donors. The photocurrent falls back to its original low level when biotinylated gold nanoparticles are added to selectively bind and quench the UCNPs via biotin-streptavidin coupling. Each UCNP shows an estimated photocurrent-to-dark current ratio of 10³ and each biotinylated gold nanoparticle causes at least 1 order of magnitude decrease of the photocurrent. Our integrated setup presents a promising platform for further development toward an optoelectronic biosensor capable of single-molecule detection.