This dataset contains transcriptomics of female golden tilefish (Lopholatilus chamaeleonticeps) collected from the Gulf of Mexico aboard R/V Weatherbird II cruises WB-1602, WB-1603 and WB-1701 from 2015-08-15 to 2016-09-09. Transcriptome analysis was performed in fifteen female (by macroscopic gonad evaluation) golden tilefish livers collected during 2015-2016 C-IMAGE demersal longline cruises in the Gulf of Mexico. These fish were caught at three stations, including one impacted by the Deepwater Horizon spill in the northern Gulf, one within the Campeche Bay oil fields, and one offshore the Yucatan peninsula, with no surrounding oil extraction activity. Differential gene expression between stations was evaluated after de novo transcriptome assembly from raw RNAseq reads. The dataset contains the location and date of sample collection. It also includes a description of fish such as health code, sex, standard length, fork length, total length, total weight, liver weight, gastrointestinal tract weight, and gonad weight. The cruise documentation was provided for R/V Weatherbird II cruises WB 1602, WB1603 and WB 1701, led by chief scientists Dr. Steven Murawski and David Hollander. This dataset supports the publication: Pulster, E. L., Gracia, A., Snyder, S. M., Deak, K., Fogelson, S., & Murawski, S. A. (2019). Chronic Sub-lethal Effects Observed in Wild-Caught Fishes Following Two Major Oil Spills in the Gulf of Mexico: Deepwater Horizon and Ixtoc 1. Deep Oil Spills, 388–413. doi:10.1007/978-3-030-11605-7_24