Human hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer-related deaths worldwide. HCC is a malignant tumor that can lead to intrahepatic and extrahepatic metastases. Intercellular adhesion molecule 1 (ICAM-1) is involved in cancer metastasis. ICAM-1 enhances cell-cell interactions by promoting adhesion and facilitating cell movement within the extracellular matrix. Moreover, ICAM-1 is more abundant in cancerous hepatocytes than in non-cancerous ones. Chemokine (C-X-C motif) ligand 1 (CXCL1) is found in diverse cancers, including melanoma, breast, lung, pancreatic, colorectal, and prostate. Several studies show a correlation between CXCL1 overexpression and poor prognosis in cancer. CXCL1 has been identified as a candidate gene that could function as a clinically relevant biomarker in HCC. However, the role of CXCL1 in cancer metastasis in HCC is poorly delineated. In this study, Gene Expression Omnibus (GEO) database analysis revealed a positive correlation between CXCL1 level and the progression and metastasis of hepatocellular carcinoma patients. CXCL1 treatment facilitates cell movement through inducing ICAM-1 expression. The Phosphoinositide 3-kinase (PI3K)/Akt/Nuclear Factor kappa B (NF-kB) signaling pathway plays a crucial role in CXCL1-regulated ICAM-1 production and cell motility. Thus, CXCL1 represents a promising therapeutic target for treating metastatic hepatocellular carcinoma.