Altogether, our results showed that (i) the cell stress machinery was activated by PLX treatment of melanoma cells; (ii) autophagy protected melanoma cells from PLX-induced cell death; (iii) the autophagic flux rate was increased in the absence of Gal-3 conferring an advantage to Gal-3-silenced cells to survive to PLX treatment. The gene discussed is LGALS3; the disease is melanoma.