Abstract: The contamination of grains with zearalenone (ZEN) not only causes huge economic losses, but also poses a significant threat to the health of humans and livestock. In order to develop an economical, green, efficient and direct biodegradation method for ZEN, the T. versicolor strain Tv-1 was used as the experimental strain, carbon sources, nitrogen sources, and laccase inducers (Cu²⁺ and by-products of grain and oil processing) were considered as influencing factors, and the activity of laccase in the fermentation broth served as the indicator. Single-factor experiments and response surface methodology were employed to determine the optimal liquid culture medium for laccase production by T. versicolor and enhance the activity of laccase in the fermentation broth. Then, the T. versicolor fermentation broth prepared under optimal medium conditions was used to directly degrade ZEN, and the effect of treatment time on the degradation rate of ZEN was investigated. The results showed that the optimal liquid culture medium for laccase production by the T. versicolor strain Tv-1 was found to have a peel potato concentration of 200 g/L,a maltose concentration of 19.30 g/L, a yeast extract concentration of 2.00 g/L, a wheat bran concentration of 42.60 g/L, and a Cu²⁺ concentration of 0.48 mmol/L. Under these conditions, the laccase activity reached 5 611.56 U/L, which was a 22.86-fold increase compared with the laccase activity in the non-optimized medium. This fermentation broth was directly used to degrade ZEN, achieving a degradation rate of 92.45% for ZEN at the 96^th hour. Therefore, this study determined the optimal liquid culture medium for laccase production by the T. versicolor Tv-1 and the fermentation broth can efficiently degrade ZEN. This lays the theoretical foundation for reducing ZEN in grains.