Subacute ruminal acidosis (SARA) is a common metabolic disease in the dairy farming industry which is usually caused by an excessive amount of high concentrate diet. SARA not only threatens animal welfare but also leads to economic losses in the farming industry. The liver plays an important role in the distribution of nutritional substances and metabolism; however, a high concentrate diet can cause hepatic metabolic disorders and liver injury. Recently, noncoding RNA has been considered as a critical regulator of hepatic disease, however, its role in the bovine liver is limited. In this study, 12 mid-lactating dairy cows were randomly assigned to a control (CON) group (40% concentrate of dry matter,
n
= 6) and a SARA group (60% concentrate of dry matter,
n
= 6). After 21 d of treatment, all cows were sacrificed, and liver tissue samples were collected. Three dairy cows were randomly selected from the CON and SARA groups respectively to perform whole transcriptome analysis. More than 20,000 messenger RNA (mRNA), 10,000 long noncoding RNA (lncRNA), 3,500 circular RNA (circRNA) and 1,000 micro RNA (miRNA) were identified. Furthermore, 43 mRNA, 121 lncRNA and 3 miRNA were differentially expressed, whereas no obvious differentially expressed circRNA were detected between the 2 groups. Gene Ontology (GO) annotation revealed that the differentially expressed genes were mainly enriched in oxidoreductase activity, stress, metabolism, the immune response, cell apoptosis, and cell proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the deferentially expressed genes were highly enriched in the phosphatidylinositol 3 kinase (
PI3K
)
-
serine/threonine kinase (
AKT
) signaling pathway (
P
< 0.05). According to KEGG pathway analysis, the differentially expressed lncRNA (DElncRNA) target genes were mainly related to proteasomes, peroxisomes, and the hypoxia-inducible factor-1 signaling pathway (
P
< 0.005). Further bioinformatics and integrative analyses revealed that the lncRNA were strongly correlated with mRNA; therefore, it is reasonable to speculate that lncRNA potentially play important roles in the liver dysfunction induced by SARA. Our study provides a valuable resource for future investigations on the mechanisms of SARA to facilitate an understanding of the importance of lncRNA, and offer functional RNA information.