C-X-C motif chemokine ligand 14 (CXCL14) has antitumor effect. Kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is activated in various tumors. The relationship between CXCL14 and Akt/mTOR pathway in hepatocellular carcinoma (HCC) remained elusive. Therefore, this paper aimed to examine their interaction in HCC. First, CXCL14 expression was determined to be low-expressed in HCC tissues and cells (SNU-423, SNU-182, SNU-387, PLC/PRF/5, HuH7, and HCCLM3). Then, CXCL14 was overexpressed in HuH7 cells and inhibited in HCCLM3 cells to help investigate the function of CXCL14 on cell viability, growth and apoptosis. Akt activator (SC79) and inhibitor (AZD5363) were used to examine the involvement of Akt pathway in hepatocellular carcinoma. Overexpressed CXCL14 suppressed cell viability and growth, but promoted the apoptosis by upregulated Bax and cleaved(C) caspase-3, donwregulated Bcl-2 and the inhibition of Akt and mTOR phosphorylation. Meanwhile, knockdown of CXCL14 imposed an opposite effect to overexpressed CXCL14. SC79 partially mitigated the functions of overexpressed CXCL14, while AZD5363 mitigated the functions of CXCL14 knockdown. To conclude, CXCL14 inhibited growth but promoted apoptosis of HCC cells via suppressing Akt/mTOR pathway, thus, CXCL14 might be a potential target for HCC treatment in clinical practice.