Objective：To design and synthesize novel tetrahydroisoquinolines with anti-fungal activities. Methods: 3,4-dimethoxyphenylethylamine was taken as the template and the title compounds were synthesized through Pictet-Spengler reaction, neutralization reaction, substitution, hydrolysis, and acylation. Results: Twelve title compounds were obtained and all of them were firstly reported. Besides, all the target compounds had anti-fungal activities. The anti-fungal activities of compounds 6~8 and 10~12 were similar to or stronger than that of fluconazole’s. Conclusion: Title compounds obtained in this study belong to a new type of anti-fungal agent, which deserves further study.