Here we demonstrate that SHMT1 is upregulated in patient-derived lung cancer tissue samples, there is a crosstalk among SHMT1 and 2 and, unlike other cancer cell types, the downregulation of SHMT1 in lung cancer cell lines through RNAi induces cell cycle arrest and apoptosis, the latter with the involvement of p53. This evidence concerns the gene SHMT1 and lung carcinoma.