St. Jerome was one of the most depicted saints in 17th-century Italian painting. The church promoted the popularity of his cult, as he was regarded as a theologian, a hermit, and a writer who was the first to translate the Bible into Latin. The painting depicts the saint in meditation, with his traditional attributes. The glasses symbolise his wisdom, the open Bible, sheets of paper, and pen represent the translation of the Holy Scriptures, and the skull serves as the sign of the transience of life. St. Jerome is depicted as half-figured with a detailed anatomy of the body. He is dressed in a red cloak, considered a cardinality symbol. The picture's composition, execution, and plot are unusual for Salvator Rosa's creative work. The signature "Salvator Rosa 80" on one of the sheets in the basket was most likely added afterwards.