We identified that inhibition of STAT3 activated MAPK and PI3K/AKT/mTOR to stimulate autophagy, leading to reduced cisplatin resistance and tumor growth/metastasis, whereas induction of p53 decreased the expression level of STAT3 (Y705) and abolished the inhibition of pSTAT3 Y705 on the endoplasmic reticulum stress signaling pathway and autophagy signaling pathway, leading to upregulation of the ERS- and autophagy-associated indicators and the chemosensitivity of cells to cisplatin treatment. The gene discussed is TP53; the disease is neoplasm.