The underlying functions of long non-coding RNAs (lncRNAs) on chemoresistance in multiple cancers have been testified. However, the function and mechanism of IncRNAs on chemoresistance in hepatocellular carcinoma are still confused. In this study, we concentrated on the function and mechanism of KCNQ1OT1 on oxaliplatin resistance in hepatocellular carcinoma. Results showed that KCNQ1OT1 was significantly up-regulated in oxaliplatin-resistant HepG2 and Huh7 cells. Moreover, knockdown of KCNQ1OT1 inhibited the cell proliferation, migration, invasion and reduced the expression of drug resistant gene (MRP5, MDR1, LRPI). Additionally, bioinformatics analysis and dual-luciferase reporter assay showed that miR-7-5p directly targeted the 3'-UTR of miR-7-5p and ABCC1 mRNA, indicating that KCNQ1OT1 regulated the expression of ABCC1 via endogenous sponging miR-7-5p. Conclusively, KCNQ1OT1 modulated oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ABCC1 axis, indicating a novel approach for the treatment of hepatocellular carcinoma. (C) 2018 Elsevier Inc. All rights reserved.