Seawater is an economical and eco-friendly alternative to chemical fertilizers because it contains various plant essential minerals required for plant growth. Seawater application has various effects on crops at the physiological and transcriptional levels. In this study, transcriptional changes in Ligularia stenocephala, a vegetable crop known as "Gondalbi", in response to deep seawater (DSW) treatment were examined using RNA sequencing. L. stenocephala was treated with 5% and 10% DSW (designated to DSW5 and DSW10) or 500X and 1000X of a fertilizer (designated to SWF500 and SWF1000) comprising filtered DSW and additional minerals. RNA sequencing generated 152 million clean sequence reads in total, of which de novo assembly generated 147,406 unigenes with an average length of 566.6 bp. The GC content of five transcriptomes was 42.95-43.65%, and the N50 was 776 bp. Annotation of all identified unigenes was performed using seven different databases, and 67,592 unigenes (45.8%) were annotated. KEGG analysis annotated total of 7009 unigenes (22.9%) into 421 pathways. Because L. stenocephala is known for its anti-oxidative properties, we focused on genes associated with natural antioxidant biosynthesis and identified several unigenes involved in the biosynthesis of glutathione, tocopherol, beta-carotenoids, flavonoids, and ascorbic acid. Furthermore, we carried out the mining of simple sequence repeat (SSR) and identified 35,280 from the L. stenocpehala transcriptome. Present data would be valuable for an enhanced understanding of the transcriptional properties of seawater application in other crops and for the investigation of the functional properties and therapeutic potential of L. stenocephala.