Genetically improved farmed tilapia (Oreochromis niloticus, GIFT) is prone to hepatic metabolic imbalance and suffer from fatty liver disease during the intensive farming. Long non-coding RNAs (lncRNAs) performed essential roles in varieties of biological processes, including lipid metabolism. However, the lncRNAs regarding hepatic lipid metabolism in tilapia have not been identified. In this study, Illumina sequencing and bioinformatic analysis was performed on the liver of male GIFT juvenile fed with high-fat diet (HFD, 18.5% lipid) or normal-fat diet (NFD, 8% lipid) for 56 days. RNA-seq analyses revealed 299 differentially expressed (DE)-mRNAs and 284 DE-lncRNAs between these two groups. The transcript expression of 16 candidates (eight DE-mRNA and eight DE-lncRNAs) was verified by qRT-PCR, and the results were consistent with those of RNA-seq. Furthermore, 65 cis targets and 3610 trans targets of DE-lncRNAs were predicted. Functional analyses suggested that multiple metabolic pathways was changed in response to high-fat intake, including PPAR signaling pathway, Fatty acid degradation and Fatty acid metabolism, among others. Co-expression networks was constructed and indicated that most lncRNAs interact with numerous mRNAs involved in lipid metabolism, and vice versa. Additionally, expression patterns analysis of three lncRNAs (MSTRG.14598.1, MSTRG.6725.3 and MSTRG.13364.2) and their potential targets (faldh, slc25a48 and fabp7a) associated with PPAR signaling pathway were investigated. Our study provides a basis for further explore the functions of lncRNAs associated with lipid metabolism in tilapia. Overall design: mRNA and lncRNA profiles of GIFT fed with HFD NFD for 56 days were generated by deep sequencing, in triplicate, using Illumina Novaseq™ 6000.