This study was to examine the effects of yeast extract (YE) and its fractions (YE1 and YE2) on the growth and diepoxin ζ (a spirobisnaphthalene with a diversity of bioactivities) production in liquid culture of Berkleasmium-like endophytic fungus Dzf12 from Dioscorea zingiberensis. When YE was applied to the liquid medium at 10 g/L on day 3 of culture, the diepoxin ζ production was most effectively enhanced 3.2-fold (378.70 mg/L versus 120.09 mg/L in control) after another 10 days culture. Feeding with 15 g/L of YE on day 9, the mycelia biomass reached 16.44 g/L, about 2.3-fold in comparison with the control (7.15 g/L). The polysaccharide fraction (YE1) was mainly responsible for stimulating diepoxin ζ accumulation, and the non-polysaccharide fraction (YE2) was mainly responsible for promoting mycelia growth. The results showed that the diepoxin ζ production in liquid culture of endophyte Dzf12 could be effectively enhanced by YE and its fractions.