Spirulina, an edible blue-green alga, has great potential for various applications in human health, possibly including reduced skin aging. The mechanisms by which spirulina crude protein (SPCP) may influence human skin fibroblast viability are not yet understood; therefore, a human dermal fibroblast cell line (CCD-986sk) was used as a cell model system to study the influence of SPCP on human skin fibroblast viability. An enzyme-linked immunosorbent assay showed that collagen formation improved in SPCP-treated cells in a dose-dependent manner, while elastase activity was decreased. In addition, western blot analysis showed a dose-dependent decrease in the expression of the aging-associated gene matrix metalloproteinase-8, a collagen-degradative enzyme. It was also shown that SPCP upregulated epidermal growth factor receptor (EGFR) activity, leading to activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. Together, these results demonstrated that SPCP increases human fibroblast viability by activation of the EGFR/MAPK signaling pathway. This contribution sheds light on the molecular mechanism for SPCP increasing the viability of human skin cell and provides a potential efficient cosmeceutical for protecting human skin.