Here, we demonstrate that: (1) FGF21 expression is decreased in both PCa tissues and cell lines; (2) FGF21 inhibits the proliferation, clone formation, migration, and invasiveness of LNCaP cells (a PCa cell line) and promotes their apoptosis; (3) FGF21 overexpression attenuates high glucose-induced LNCaP cell proliferation and apoptosis; (4) FGF21 is related to autophagy and the PI3K–Akt–mTOR pathway; and (4) FGF21 increases autophagy by inhibiting the PI3K–Akt–mTOR signaling pathway. The gene discussed is AKT1; the disease is posterior cortical atrophy.