Objective: To investigate the effect of COTE1 gene on hepatocarcinoma cell line PLC/PRF/5 apoptosis induced by doxorubicin(DOX). Methods: The expression level of COTE1 mRNA and protein were detected by qPCR or Western blotting after transfected with COTE1 shRNA lentivirus.CCK-8 assay was used to detect the inhibition rate of DOX on the proliferation of HCC cells.The apoptosis rate of HCC cells treated with DOX was detected by flow cytometry. Results: qPCR and Western Blotting results showed the expression of COTE1 was down-regulated after transfection with lentivirus and CCK-8 results showed the inhibitory effect of DOX was increased. Flow cytometry results showed that DOX could promote the apoptosis rate, while inhibition of the expression of COTE1 can enhance the apoptosis rate.Conclusion: Inhibition of COTE1 could enhance the sensitivity of PLC/PRF/5 cells to doxorubicin by enhancing apoptosis.