In conclusion, we identify a novel HNF4α/lnc‐APUE/miR‐20b/E2F1 regulatory axis and disclose its potential functions, that is, downregulation of HNF4α may lead to the upregulation of lnc‐APUE in HCC, whereas lnc‐APUE may work as a cellular sponge to bind miR‐20b and relieve its repression on E2F1 expression, resulting in an increase of E2F1 level and in turn accelerating the G1/S transition and cell proliferation. Here, HNF4A is linked to hepatocellular carcinoma.