Abstract: By taking the griseofulin-producing strain ji-2 as the original strain, the strain UL100-80 with high potency of griseofulvin and short fermentation period was selected after the mutagenesis with ultraviolet ray and lithium chloride. The potency of the strain UL100-80 was 91 304 μg·mL^-1,which was 47.8% higher than that of the original strain ji-2, and the genetic stability was good through the continuous subculture. The fermentation conditions of UL100-80 were optimized, and the optimized liquid fermentation medium was as follows:rice flour 150 g·L^-1, NaCl 8.0 g·L^-1, CaCO₃ 8.0 g·L^-1, soybean powder 1.0 g·L^-1, KH₂PO₄ 6.0 g·L^-1, KCl 7.0 g·L^-1, NaNO₃ 1.0 g·L^-1, FeSO₄ 1.0 g·L^-1, and pH was natural. The optimized culture conditions were as follows:the seed solution cultured for 40 h was inoculated at 12% dose, and cultured at 28℃ for 12 d. The potency of griseofulvin was increased from 91 304 μg·mL^-1 before the optimization to 124 965 μg·mL^-1, with an increase of 36.9%. While compared with the original strain ji-2, the potency of griseofulvin produced by UL100-80 increased by 1.02 times, and the fermentation time was shortened by 48 h.