Flounder is a promising model species for environmental monitoring of coastal regions. To assess the usefulness of liver transcriptome profiling, juvenile olive flounder Paralichthys olivaceus were exposed to two pollutants, bisphenol S (BPS) and benzo[a]pyrene (BaP), which have different chemical characteristics and have distinct modes of metabolic action in teleost. Six hours after intraperitoneal injection with BPS (50 mg/kg bw) or BaP (20 mg/kg bw), liver transcriptomes were analyzed using the Illumina Hiseq 3000 platform. Interestingly, the transcriptome was highly sensitive and was distinctively expressed in response to each chemical. The primary effect of BPS was significantly increased transcription of egg process and vitellogenesis related genes, including vitellogenins (vtg1, vtg2), zona pellucida sperm-binding proteins (zp3, zp4), and estrogen receptors (erα, erβ), with increases in plasma 17β-estradiol (E2) and vitellogenin (VTG) concentrations. Following BaP treatment, detoxification- and biotransformation-related genes such as cyp1a1 and UDP-glucuronosyltransferase (ugt1a1) were significantly increased, with an increase in EROD activity. In both transcriptomes, mRNA expression of genes involved in antioxidant defense systems was increased, while genes involved in innate immunity were decreased upon BPS or BaP exposure with a decrease in complement activity. This study provides useful insight into the chemical-specific hepatic transcriptional response of P. olivaceus and suggests a basis for further studies examining biomarker application of liver transcriptomes for environmental pollution.