Epigenetics is the study of heritable changes in gene expression without changing the DNA sequence - a change in phenotype without a change in genotype. Epigenetic abnormalities can lead to serious diseases such as cancer in organisms. Histone methylation is one of the several manifestations of epigenetics, and requires specific enzymes to catalyze, for example, G9a, which is a histone methyl transferase. G9a catalyzes the methylation of histone 3 lysine 9 (H3K9) and histone 3 lysine 27 (H3K27). In addition, G9a also plays an essential role in DNA replication, damage and repair, and gene expression by regulating DNA methylation. Moreover, G9a has been found to be overexpressed in many tumor cells and is associated with the occurrence and development of tumors. Because of its unique characteristics, G9a has become a very promising target for anti-cancer agents. Over the last decade, dozens of G9a inhibitors have been discovered as potential anticancer therapeutic agents. In this review, we summarize and classify current G9a inhibitors, the challenges and future direction are also discussed in detail.