Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers in the human population. HCC is an inflammation-associated cancer caused by different etiological factors. The chronic inflammation leads to continuous cycles of hepatocytes destructive-regenerative process and contributes to HCC initiation and progression. Macrophages play a crucial role in chronic liver inflammation. The tumor microenvironment plays a key role in the progression of HCC. Tumor-associated macrophages are a well-known component of the tumor microenvironment and abundantly infiltrate HCC microenvironment. The roles of macrophages in the development and progression of HCC have been recognized. The deep understanding of macrophages in HCC will be critical for developing effective HCC therapy. Targeting of macrophages might provide novel therapeutic approaches for HCC patients and is an emerging field of interest. This review summarizes the knowledge on the contribution of macrophages in the development and progression of HCC, as well as potential immunotherapy being explored in targeting macrophages.