China has had a high prevalence of hepatitis B virus infection (HBV) infection since the 20th century. Vertical mother-to-child transmission always leads to family aggregation of HBV infection. This study investigated the HBV infection status of a four-generation family by telephone consultation and review of outpatient and hospitalization medical records. The first generation consisted of 1 female relative born in 1906 who died of ascites due to cirrhosis at 60 years of age. The second generation consisted of 4 people born between the 1920s and 1930s. All of them had an HBV infection. One male relative died from ascites due to cirrhosis at 43 years of age. One female relative, aged 90 years, was an HBV carrier. Her liver function had been normal for a long time. Another female relative, aged 86 years. She had hepatic failure at age 40 years.One female relative died from liver cancer at age 66 years. The third generation consisted of 13 people. Six people had HBV infection, of whom 5 were male and one was female. One male relative died from liver cancer at age 48 years. Another male relative was diagnosed as having cirrhosis at 45 years old. The fourth generation consisted of 21 people, none of whom had an HBV infection. They were born between the 1960s and 1980s. Conclusions: This four-generation family has an obvious family aggregation of HBV infection. The infection rate was higher and the infection severity was greater in males than in females. The spread of HBV infection in this family was reduced in every succeeding generation.