A physical unclonable function (PUF)-based method for enhancing system reliability is provided, including: requesting, by a client, data transmission with a server; randomly selecting, by the server, a plurality of metal oxide semiconductor (MOS) devices in an MOS array, and acquiring positional information of the plurality of MOS devices; calculating, by the server, a probabilistic PUF that the trap in each of the plurality of MOS devices is occupied by a carrier and constructing a probabilistic model; randomly generating, by the server, detection time according to the probabilistic model and sending the detection time and the positional information to the client; and determining, by the server, an occupancy probability of the trap in each of the plurality of MOS devices at the detection time according to the probabilistic model, and generating a theoretical code key.