ABSTRACT: Feed efficiency (FE) is essential for pig production. In this study, 300 significantly differentially expressed (DE) transcripts, including 232 annotated genes, 28 cis-natural antisense transcripts (cis-NATs), and 40 long noncoding RNAs (lncRNAs), were identified between the liver of Yorkshire pigs with extremely high and low FE. Among these transcripts, 25 DE lncRNAs were significantly correlated with 125 DE annotated genes at a transcriptional level. These DE genes were enriched primarily in vitamin A (VA), fatty acid, and steroid hormone metabolism. VA metabolism is regulated by energy status, and active derivatives of VA metabolism can regulate fatty acid and steroid hormones metabolism. The key genes of VA metabolism (CYP1A1, ALDH1A2, and RDH16), fatty acid biosynthesis (FASN, SCD, CYP2J2, and ANKRD23), and steroid hormone metabolism (CYP1A1, HSD17B2, and UGT2B4) were significantly upregulated in the liver of high-FE pigs. Previous study with the same samples indicated that the mitochondrial function and energy expenditure were reduced in the muscle tissue of high-FE pigs. In conclusion, VA metabolism in liver tissues plays important roles in the regulation of FE in pigs by affecting energy metabolism, which may mediate fatty acid biosynthesis and steroid hormone metabolism. Furthermore, our results identified novel transcripts, such as cis-NATs and lncRNAs, which are also involved in the regulation of FE in pigs.