The invention relates to a medicine combination and the application thereof in preparing preparations for treating chronic hepatitis B. The combination comprises a medicine combination with polysaccharide nucleic acid of bacillus calmette guerin as the active component and a Chinese traditional medicine combination, wherein the Chinese traditional medicine combination is prepared from astragalus, herba artemisiae scopariae, oldenlandia diffusa, herba lysimachiae, codonopsis pilosula, processed polygonum capitatum, salvia, radix paeoniae alba, chinaberry fruit, taraxacum, cortex moutan, poria and atractylodes; the polysaccharide nucleic acid of bacillus calmette Guerin is nonspecific immunity active reinforcer, and can effectively restrain the reproduction of hepatitis virus and promote the rapid negative turning of HBV-DNA and HbeAg; and the Chinese traditional medicine combination has the efficacy of invigorating qi and spleen, promoting blood circulation by removing blood stasis and clearing away heat and toxic material. The medicine combination can reduce the incidence rate of variation and drug resistance and effectively promote the improvement under the condition of improving the healing efficacy, and provides a novel, safe and effective drug choice for clinics.