Objective: To investigate the correlation between the virus load and hepatitis B virus large surface protein(LHBs)in serum from chronic hepatitis B patients with e antigen negative,so as to evaluate whether LHBs can be used as a marker to determine the replication extent of hepatitis B virus in patients with negative hepatitis B e antigen(HbeAg). Methods: Sera from 83 chronic hepatitis B patients with HBeAg negative were collected. LHBs level was detected by ELISA,with HBeAg tested by automatic immune analyzer and HBV DNA analyzed by real-time fluorescent quantitative PCR method. The correlation between the detection rates of LHBs in three groups (HBV DNA no-copy group,low-copy group and high-copy group) and the copy number of HBV DNA was analyzed. Results: In HBV DNA no-copy group,the positive rate of LHBs was 6.38%;in low-copy group,the positive rate was 56.25%,and the logarithm of copy number didn’t have statistical correlation with the absorbance values of LHBs in those two groups(r = 0.25,P = 0.36);in high-copy group,the positive rate was 56.25%,and there was significant correlation between the logarithm of copy number and the absorbance value of LHBs(r = 0.90,P < 0.0001). Conclusion: The detection of LHBs in chronic hepatitis B patients with HBeAg-negative contributes to evaluate the replication extent of HBV in patients. However,whether it can be used as an effective marker to guide the antiviral therapy of HBeAg-negative patients remains to be further studied.