The flotation separation of galena from sphalerite was commonly implemented under pH > 10.5, which led to the consumption of lime. In this paper, 2-diethylamine-4-hydroxy-1,3,5-triazine-6-thiol (DEHTT) was synthesized and introduced as a highly selective collector to perform the depressant-free flotation separation of Pb/Zn sulfide minerals. The microflotation results indicated that 8.0 × 10 −7 mol/L DEHTT recovered 94.17% galena and 26.67% sphalerite from their mixture at pH 8.5 regulated by Na 2 CO 3 , and under the same conditions, sodium isobutyl xanthate (SIBX) floated out 94.94% galena and 50.41% sphalerite, deducing a superior flotation selectivity of DEHTT in comparison to SIBX. In situ AFM images displayed the more preferable adsorption of DEHTT on galena in comparison to that on sphalerite. The results of adsorption thermodynamics and kinetics inferred that the adsorption of DEHTT onto the galena surface was a spontaneous endothermic chemical process. XPS further indicated that DEHTT combined with interface Pb atoms to form the −S−Pb and −O− Pb bonds. The special affinity of DEHTT to galena achieved the selective flotation separation of galena from sphalerite without the addition of lime and depressants.