Biomolecule detection was achieved using a Si single-electron transistor (SET) for highly-sensitive detection. A multiple-island channel-structure was used for the SET to enable room-temperature operation and to increase sensitivity. Coulomb oscillation shifted against the gate voltage due to biotin-streptavidin binding. Coulomb oscillation has a possibility to increase transconductance (gm), and a higher gm leads to greater sensitivity to a charged target. Since a Si structure is important for integrating label-free-biomolecule and/or ion sensors into large-scale-integrated circuits, a Si SET with multiple islands should enable the integration of a sensor system on a single chip for multiplexed detections and simultaneous diagnoses.