These results clearly indicated that YY1 could regulate HCC cell lipid accumulation through PGC-1β/MCAD and PGC-1β/LCAD axis even when HIF-1α was absence, suggesting the presence of HIF-1α-independent pathway in YY1 regulation of PGC-1β-induced fatty acid β-oxidation. Here, PPARGC1B is linked to hepatocellular carcinoma.