Precursor messenger RNA processing factor 19 (PRP19) is known to be a critical component of the eukaryotic spliceosomal machinery and DNA damage repair system, the deregulation of which leads to many disease conditions. In many human cancers, PRP19 expression is upregulated, but its functional significance and corresponding underlying mechanisms remain to be addressed. Focusing on lung carcinomas, PRP19 upregulation was achieved by plasmid transfection into A549 adenocarcinoma cells. The transfected cells were then subjected to several in vitro and in vivo assays following in situ assessment of the protein in paired clinical lung tissues. We report that PRP19 expression is elevated in lung carcinoma tissues compared to non-tumor tissues. Following its upregulation, PRP19 repressed cell proliferation and tumor growth by upregulating the expression of the cell cycle arrest protein p21.