Avian influenza H7N9 viruses are an important public health concern due to their high mortality rate and potentials for future pandemics. We investigated human susceptibility to H7N9 viruses using recombinant H7N9 hemagglutinin (HA) proteins as a probe and found a strong association between H7N9 infections and HA binding among saliva samples from 32 patients and 60 uninfected controls in Jiangsu province, China, during the 2016 epidemic season. We also found that sialyl Lex (SLex) antigen that was recognized by H7N9 HA was associated with H7N9 virus infection. Further analysis suggested that additional saccharide residues adjacent to the SLex moiety may affect the H7N9-binding specificity. Our data suggested that saliva may be a useful reagent to study human susceptibility to avian influenza H7N9 virus, which may impact the disease control and prevention of avian influenza viruses as important human pathogens.