Abstract： Objective To investigate the effects of baicalein and acitretin on the apoptosis in a human cutaneous squamous cell carcinoma cell line, SCL-12. Methods Cultured SCL-12 cells were treated with different concentrations of baicalein (3.125, 6.25, 12.5 μmol/L) and acitretin (2.5, 5.0, 10.0 μ mol/L), alone or in combination, for 48 hours. Subsequently, cell proliferation was detected by MTT assay, and cell apoptosis by ELISA as well as annexin V-FITC and propidium iodide double staining. Real-time quantitative RT-PCR was used to detect the expression of Fas mRNA in SCL-12 cells. Results The cell proliferation of SCL-12 cells was inhibited by baicalein and acitretin alone or in combination. The combination of baicalein and acitretin at the three tested concentrations, except for that of baicalein at 3.125 μmol/L and acitretin at 2.5 μmol/L, more strongly inhibited the proliferation of SCL-12 cells compared with baicalein or acitretin alone, and the inhibitory effect was in a dose-dependent manner. The early apoptosis rate was 9.39% ± 1.52%, 20.86% ± 2.16%,36.85% ± 3.26% in SCL-12 cells treated with baicalein of 3.125 μmol/L, acitretin of 5.0 μmol/L alone and their combination, respectively, significantly higher than that in untreated cells (4.39% ± 0.64%, all P <0.05); the induction of apoptosis in SCL-12 cells by the combination of baicalein and acitretin was stronger than that by baicalein or acitretin alone (F = 138.44, P < 0.05). Baicalein and acitretin alone or in combination significantly increased the mRNA expression of Fas in SCL-12 cells, and the effect of their combination was stronger than that of baicalein or acitretin alone. Conclusions Baicalein and aeitretin could inhibit the growth of and induce the apoptosis in SCL-12 cells, and the effect is enhanced by the combination of baicalein and acitretin, which may be associated with the upregulation of Fas expression in SCL-12 cells.