Abstract:“Artificial Base” is also known as “Expanded Genetic Alphabets”. Through modifying normal bases, it is designed to achieve the function of native nucleic acid, which was first introduced about thirty years ago. In 2014, Nature reported a semi-synthetic Escherichia coli, whose genome contains a pair of unnatural base pair which can be stably propagated in the semi-synthetic bacterium. This landmark work was selected as one of the top ten breakthroughs of 2014 by the Science journal. Here, we panoramically review the representative achievements in the field of artificial base and synthetic life, particularly two leading artificial base pairs respectively with alternative hydrogen bonding pattern and hydrophobic shape complementation pattern. Moreover, we discuss the significant work regarding the synthetic living system with sixletter nucleotides and its effect on future developments of synthetic biology. The successful applications of diagnostic kit for DNA test and other cases are also introduced. Finally, we discuss the further work required to this field and the challenges.