Folic acid, also know as pteroymonoglutamic acid and vitamin M, is one of the important constituents of vegetables and fruits. 5-methyltetrahydrofolate is the biologically active form of folate, and acts as carriers of one-carbon moieties for many biological processes, such as synthesis of nucleotide and proteins and epigenetic modification. Epigenetic modification plays an important role in the tumorigenesis. Recent epidemiological studies indicate that folic acid deficiency in vivo has a close correlation with tumorigenesis. Folate deficiency may induce tumorigenesis via global DNA hypomethylation and internal specific nucleotide site hypermethylation, finally leading to tumorigenesis. This review mainly focused on the correlation of folic acid deficiency with tumorigenesis.