The effects of lycopene, genistein, and epigallocatechin-3-gallate (EGCG) on cell viability were tested in vitro using a normal human skin fibroblast (NHSF) cell line (CRL-1474) and granulation tissue fibroblasts (GTFs) obtained from a patient with middle ear cholesteatoma. Cell cultures were added with lycopene (1, 5, and $10;{mu}M$), genistein (1, 5, 10, 25, and $50;{mu}M$), and EGCG (1, 5, 10, 25, and $50;{mu}M$) and their respective control cultures were established by adding 5 mL/L tetrahydrofuran (THF), 5 mL/L dimethyl sulfoxide (DMSO), and 5 mL/L DMSO. A colorimetric assay was employed for determining cell viability using thiazolyl blue tetrazolium bromide. Cell viability was expressed as a percentage of the control. Data were analyzed using two-way analysis of variance separately for each compound. Lycopene addition decreased viability of NHSFs and GTFs compared with THF addition (64.1%, 60.5%, and 100%, respectively, P < .0001). Genistein addition also increased viability of both NHSFs and GTFs compared with DMSO addition (P < .02). Increasing EGCG concentration tended to cause a linear increase in viability of NHSFs but did not alter viability of GTFs (P < .10). Our data suggest that genistein and EGCG but not lycopene could help maintaining or improving skin health through enhancing viability of skin fibroblasts.