Contamination with polycyclic aromatic hydrocarbons (PAHs) causes noticeable ecological problems in aquatic ecosystems. 9,10-phenanthrenequione (9,10-PQ) is an oxidized PAH and is highly toxic to aquatic animals. However, the effects of 9,10-PQ on the molecular metabolism of fish remain largely unknown. In this study, Takifugu obscurus juveniles were acutely exposed to 44.30 µg/L 9,10-PQ for three days. The transcriptome profile changes in their livers were compared between the 9,10-PQ treatment group and the control using T. rubripes as the reference genome. The results identified 22,414 genes in our transcriptome. Among them, 767 genes were differentially expressed (DEGs) after exposure to 9,10-PQ, which enriched 16 KEGG pathways. Among them, the glycolysis, phagosome, and FOXO signaling pathways were significantly activated in 9,10-PQ treatment compared with the control. These data indicate that 9,10-PQ increased the glycolysis capacity to produce more energy for resistance and harmed immune function. Moreover, several genes related to tumorigenesis were significantly up-regulated in response to 9,10-PQ, displaying the carcinogenic toxicity of 9,10-PQ to T. obscurus. Genes in steroid biosynthesis pathways were down-regulated in the 9,10-PQ treatment group, suggesting interference with the endocrine system. Overall, these findings provide information to help evaluate the environmental risks that oxygenated-PAHs present to T. obscurus.