We then used small interfering (siRNA) to knock down the KRT8 expression in chordoma cells followed by chemotherapy both in vitro and in vivo, and the results showed that knockdown of KRT8 overcomes chemoresistance of the chordoma cells through aggravating ER stress, through the PERK/eIF2α arm of UPR and thereby blocking autophagy. Here, EIF2AK3 is linked to chordoma.