Hydroxyl radical (•OH) is an important marker of the progress of heavy metal induced oxidative stress. However, most reported probes and detection methods cannot meet the need of monitoring the •OH concentration within the whole progress because of the limited linear range. Besides, a low detection limit, high sensitivity, and good selectivity were also required. In this study, an ultrahigh sensitivity multifunctional nanoprobe (ICG-modified NaLuF4:Yb,Er) was developed to evaluate heavy metal induced oxidative stress by detecting •OH concentration, with a colorimetric, upconversion luminescence, and photothermal stepped method. This method has a broad linear detection range, from 16 pM to 2 μM, and a low detection limit of 4 pM. Besides, the nanoprobe showed less response to ions, amino acids, biomolecules, and other radical oxygen species (H2O2 and O2-) than •OH. This highly selective, highly sensitive probe with a broad linear detection range has great potential utility for monitoring •OH concentration in live hypatocyte within the progress of heavy metal induced oxidative stress, with probable in vivo applications in the future.