Legionella pneumophila is an intracellular, Gram-negative bacterium and the causative agent of Legionnaires’ Disease. Legionella uses a type-IVB Dot/Icm secretion system that is essential for bacterial survival and intracellular replication. The Dot/Icm secretion system injects over 300 “effector” proteins into the host cell which hijack various cellular processes to establish infection. Legionella effectors target host proteins using an arsenal of post-translational modifications but effectors that act on host nucleic acids, DNA or RNA, have remained unknown. To isolate Legionella effectors that bind host RNA, we performed RNA-interactome capture (RIC) of poly(A)-tailed eukaryotic mRNA during infection of a macrophage cell line and then identified RNA-binding proteins using mass spectrometry. This study identified a number of Legionella effectors as putative RNA-binding proteins, including a novel GTPase-activating protein (GAP) involved in mRNA processing and transport. Together, our data suggests that Legionella effectors not only post-translationally target the host proteome during infection but also post-transcriptionally target RNA and directly regulate the host epitranscriptome.