The invention relates to the application of a medicine combination in preparing a preparation for treating chronic hepatitis B. The medicine combination uses polysaccharide nucleic acid of bacillus calmette Guerin as the active component; the polysaccharide nucleic acid of bacillus calmette Guerin is a nonspecific immunity active reinforcer, and can effectively restrain the reproduction of hepatitis virus and promote the rapid negative turning of HBV-DNA and HbeA. The invention has the advantages of low price, high safety, high adaptability, rapid effect, long effect maintenance time and low drug resistance in treating the chronic hepatitis B.