Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a host ligand that is believed to play an important role in rotavirus host susceptibility and host range. In this study, paired fecal and saliva samples collected from children with viral gastroenteritis, as well as paired serum and saliva samples collected from the general population in south China were studied to evaluate potential association between rotavirus infections and human HBGA phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8] rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the rotavirus-infected children were determined through their saliva samples. Secretor statuses were found to correlate with the risk of rotavirus infection and all P[8]/P[4] rotavirus infected children were secretors. Accordingly, recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific IgG and host Lewis and secretor phenotypes has been found among 206 studied serum samples. Our study supported the association between rotavirus infection and the host HBGA phenotypes, which would help further understanding of rotavirus host range and epidemiology.