In view of the need to find new and effective therapies for HCC treatment, here we have demonstrated that the conditioned medium isolated from human amniotic membranes has valuable antiproliferative properties: AM-CM was able to inhibit DNA synthesis, cell viability, and cell cycle progression involving a decrease in Ki-67 and Cyclin D1 expression, and the upregulation of p53 and p21 expression together with the modulation of pro and antitumoral miRs. The gene discussed is CCND1; the disease is hepatocellular carcinoma.