Hepatocellular carcinoma (HCC) is a major fatal cancer that is known for its high recurrence and metastasis. An increasing number of studies have shown that the tumor microenvironment is closely related to the metastasis and invasion of HCC. The HCC microenvironment is a complex integrated system composed of cellular components, the extracellular matrix (ECM), and signaling molecules such as chemokines, growth factors, and cytokines, which are generally regarded as crucial molecules that regulate a series of important processes, such as the migration and invasion of HCC cells. Considering the crucial role of signaling molecules, this review aims to elucidate the regulatory effects of chemokines, growth factors, and cytokines on HCC cells in their microenvironment to provide important references for clarifying the development of HCC and exploring effective therapeutic targets.