In this study, we reveal the protective role of SSP in drug-induced acute or chronic liver injury and demonstrate the regulatory mechanism of SSP during damage process, in which MAPK13 phosphorylates PHGDH, the rate-limiting enzyme of SSP, at S371 upon oxidative stress and activates CMA-mediated protein degradation of PHGDH, thereby inhibiting SSP flux. Here, PHGDH is linked to injury.