The HA is present in almost all vertebrates and plays a critical role in tissue development and cell proliferation, it has been demonstrated to promote wound healing and involved in angiogenesis and inflammation. Also polynucleotydes (PN) have proved to promote the “in vitro” growth and activity of human fibroblasts and osteoblasts, to increase reparation on UVB damaged dermal fibroblasts and seems to promote proliferation of human pre-adipocytes. Several in vivo studies have demonstrated the PN effect also in vivo, inducing an increase of angiogenesis and healing process. In this paper we have evaluated the effect of a mixture of Polynucleotides (PN) and entire Hyaluronic Acid (HA) on cultured human fibroblasts by analyzing cell growth. Different mixture have been tested and it has been demonstrated that the presence of HA even at low concentration (1 mg/ml) determine an increase of PN activity up to 20%. Furthermore, the addition of HA 1 mg/ml to PN 100 μg/ml induces a cell growth rate comparable to that exerted by PN concentration of 12 μg/ml.