This chapter aims to analyze in depth the molecular pathways driving the development of hepatocellular carcinoma (HCC) in low- and middle-income countries (LMICs). HCC is a liver cancer that commonly originates from the liver itself. It has a significant global health burden, especially in resource-constrained settings. So, understanding the complicated molecular processes that cause HCC to grow in these situations is very important for making progress in effective ways to prevent it, find it early, and tailor treatment plans. This paper also looks at some important changes that happen at the molecular level during the development of hepatocarcinogenesis. These include alterations in genes and epigenetics, malfunctioning signaling pathways or networks, and risk factors unique to LMICs. It further provides insights into the candidate biomarker identification process and potential therapy targets specific to these sites only. In summary, this article will give readers, whether they are researchers, healthcare providers, or policymakers, an understanding of the different steps involved in the pathogenesis of liver cancer within poor nations, thus enabling them to take care more effectively of patients under their management while at the same time improving outcomes generally in such environments.