Abstract: Lycopene has shown good antioxidant activity due to its special structure, in addition to its good physiological functions in scavenging free radicals, inhibiting cancer cell proliferation, inducing apoptosis, anti-inflammatory and prevention of cardiovascular system diseases. In this experiment, the fermentation of lycopene was carried out using a microbial fermentation method, in which Blakeslea trispora (B. trispora) was selected as the fermenting strain and four different cyclase blockers were added to improve the production of lycopene by fermentation of B. trispora. Four cyclase blockers, such as 2-amino-6-methylpyridine, 2,6-dimethylpyridine, 2-methylimidazole and 2-isopropylimidazole, were compared for lycopene yield after fermentation, and lycopene yield was used as a screening index to select the best cyclase blocker for the next experiment. The addition of cyclase blocker increased the lycopene yield to a certain extent compared to the blank control group without the addition of the cyclase blocker, while the highest lycopene yield was obtained when 2-amino-6-methylpyridine was used as the blocker at an addition level of 0.5 g/L. Thus, 2-amino-6-methylpyridine was selected for the subsequent experiment. The effect of the addition of 2-amino-6-methylpyridine on the lycopene yield was investigated. The optimum fermentation conditions were obtained on the basis of single-factor orthogonal tests:the addition of 2-amino-6-methylpyridine at 0.4 g/L, the fermentation time with addition of 42 h, and the fermentation time of 144 h. Under these conditions, although the biomass of the bacteria decreased from 39.88 g/L to 38.85 g/L, the lycopene production increased from 7.18 mg/L to 498.59 mg/L, indicating that the yield was significantly increased. The results showed that cyclase blockers positively affected the production of lycopene by fermentation of B. trispora and significantly enhanced its yield.