Herein, from the above-mentioned findings, we hypothesize that the JMJD6–BRD4 complex may mediate HOTAIR expression, which in turn affects the radioresistance of liver cancer by interacting with LSD1. To address this hypothesis, we studied the correlation between JMJD6–BRD4 complex and HOTAIR expression in clinical tissue samples of liver cancer patients, LCSCs and xenograft tumor in nude mice, as well as the effect of their interactions on the radioresistance of LCSCs, aiming at clarifying the mechanistic actions of HOTAIR and providing a novel therapeutic target for liver cancer. This evidence concerns the gene HOTAIR and liver cancer.