Abstract Vitamin C (ascorbic acid), a water-soluble micronutrient present in fruits and vegetables, is important for multiple biological functions. Vitamin C is used as an anti-aging agent because of its collagen enhancing effects. The precise cellular signaling mechanism of vitamin C is not well known. Here we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs were treated with vitamin C before 2 hours of LL-37 treatment. Vitamin C, at 0.5mM concentration, enhances collagen mRNA expression and total soluble collagen production inhibited by LL-37. H2O2 decreased the expression of COL1A1, COL1A2, and COL3A1 mRNA, as was collagen production. We found that collagen expression and production reduced by LL-37 were increased by N-acetyl-L-cysteine (NAC). These results indicate that ROI levels are involved in collagen expression. Furthermore, vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37.