Mixed infection with hepatitis E virus (HEV) in patients with chronic hepatitis B virus (HBV) infection is frequent. HEV mixed infection often leads to activation of hepatic pathological changes and worsens the inflammatory activity. However, it is not known clearly how these two types of virus influence each other in human body. Intensive investigation has revealed that HEV mixed infection inhibits HBV replication. We have just encountered a relative rare case. The patient who was a HBV carrier and was infected by HEV. Before he was infected by the HEV, the measurement of his HBV DNA fixed quantity examination on fluorescence was <10³ copies/ml; his routine biochemistry was normal; and his anti HEV-IgM and anti-HEV-IgG appeared to be negative reaction. After he was infected by HEV, his routine biochemistry increased, and the measurement of his HBV DNA fixed quantity examination on fluorescence was 8.51 × 10⁵ copies/ml. It indicated that the replication of HBV was activated after the patient infected HEV. Finally, he was dead. This case revealed that HEV mixed infection may activate the replication of HBV, not inhibit HBV replication, and demonstrated the needs for further studies about the mechanism of the interaction of the two viruses.