A heteropolysaccharide from Gracilaria lemaneiformis named GLHP has been isolated by sulfuric acid, protein removal, dialysis, and vacuum freeze-drying. Its structure was identified and provided by Bo Rui Saccharide Biotech Co Lid, and its average molecular weight was 47600 Da. The results indicated that polysaccharides were composed of guluronic acid, mannose, ribose, rhamnose, glucosamine, galactosamine, glucose, galactose, arabinose and fucose. The top two most abundant compounds were galactose (62.08%) and glucosamine (14.72%). GLHP mainly contained three kinds of linkage type units as →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→ and →4)-β-D-Galp-(1→. The structural characterization of GLHP is →4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→4)-β-D-Galp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→. Itcould significantly reduce the UVA-induced melanogenesis in the human melanoma cells and keratinocyte cells. The tyrosinase activity experiment revealed that it inhibited the tyrosinase activity and the melanogenesis in UVA-stimulated melanoma cells. Furthermore, immunofluorescence experiment uncovered that it inhibited the migration of MLANA in UVA-induced A375 and HaCaT cells. Western blot analysis demonstrated that GLHP inhibited the UVA-induced melanogenesis in melanoma cells by blocking the binding of α-MSH and MC1R and downregulating the expressions of tyrosinase (TYR) and microphthalmia-associated transcription factor (MITF). In conclusion, our results found a novel anti-pigmentation agent could be used in cosmetics and illustrated an in-depth analysis on molecular mechanisms upon GLHP.