δ-tocotrienol induced cytotoxicity and apoptosis on melanoma cells but not on non-cancerous melanocytes. δ-tocotrienol activated the caspase 4 and upregulated the ERS markers (Grp78, PERK, phosphor- eIF2α & IRE1α) and ERS-related apoptosis markers (ATF4, CHOP & ERO1α).δ-tocotrienol induced nuclear translocation of CHOP and ATF4 and upregulated the CHOP and IRE1α mRNA.Salubrinal protected the melanoma cells from δ-tocotrienol-induced ERS-mediated apoptosis. Here, HSPA5 is linked to melanoma.