The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process. Specific chromosome losses and corresponding inactivation of tumor suppressor genes (TSGs) are frequently detected during the development of HCC. A high frequency of loss on chromosome 4q in HCC has been reported, suggesting that the dysfunction of specific TSGs on this chromosome arm is involved in the development and progression of HCC. In this article, we reviewed the studies on chromosomal loss of 4q in HCC patients using cytogenetic and molecular genetic technologies, such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analysis; we also summarized the regions of chromosome 4q with high frequency of loss in HCC patients from different countries, and discussed their relationships with clinical parameters including hepatitis B virus (HBV) infection, tumor differentiation and tumor size, and listed potential TSGs on chromosome 4q in HCC patients.