Abstract: Objective To investigate the molecular mechanism of the synergy between tetrandrine and fluconazole against Candida albicans . Methods The non-cytotoxic concentrations of tetrandrine, and the minimal inhibitory concentrations of fluoconazole alone and in combination with tetrandrine for C.albicans were determined in previous studies. A total of 16 strains of C.albicans were divided into three groups: fluconazole-susceptible group （n = 11）, dose-dependent fluconazole-susceptible group （n = 3） and fluconazole-resistant group （n = 2）. The C.albicans strains were cultured and treated with tetrandrine. RT-PCR was used to detect the expressions of efflux pump genes including MDR1, FLU1, CDR1 and CDR2 in these three groups of C.albicans before and after 24 hours of culture with or without the treatment of tetrandrine. Results Before the exposure to tetrandrine, the expressions of MDR1, FLU1, CDR1, CDR2 were significantly lower in fluconazole-susceptible C.albicans strains than in dose-dependent fluconazole-susceptible and fluconazole-resistant strains （F = 8.54, 11.16, 16.52, 14.61, all P < 0.05）. The 24-hour exposure to tetrandrine significantly decreased the expressions of MDR1 in fluconazole-resistant C.albicans strains, FLU1 in fluconazole-susceptible and fluconazole-resistant strains, and CDR1 as well as CDR2 in all the three groups of C.albicans strains （P < 0.05 or < 0.01）. Conclusion The molecular mechanism for the synergy between tetrandrine and fluconazole against C. albicans in vitro may be related to the down-regulation of MDR1, FLU1, CDR1 and CDR2 expressions.