**Abstract**

In this chapter, we present the founding framework of a novel theory termed as Cancer Evolution-Development (*Cancer Evo-Dev*), based on the current understanding of hepatitis B virus (HBV) induced hepatocarcinogenesis. The interactions of genetic predispositions and HBV infection is responsible for the maintenance of chronic non-resolving inflammation. Under the inflammatory microenvironment, pro-inflammatory factors trans-activate the expression of cytidine deaminases and suppress the expression of uracil DNA glycosylase. The imbalance between the mutagenic forces and mutation-correcting forces facilitates the generations of somatic mutations, viral mutations, and viral integrations into the host genomes. The majority of cells with genomic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of the mutated cells adapted to the hostile environment can survive, retro-differentiate, and function as cancer-initiating cells, representing a process of "mutation-selection-adaptation". *Cancer Evo-Dev* lays the theoretical foundation for understanding the mechanisms by which chronic infection of HBV promotes hepatocarcinogenesis. This theory also plays an important role in specific prophylaxis, prediction, early diagnosis, and targeted treatment of cancers.

**Keywords:** Hepatocarcinogenesis, hepatitis B virus, inflammation, mutation, evolution
