This study was conducted to determine the prevalence, species and risk factors of Cryptosporidium infection in children hospitalized for diarrhea in Guangzhou region of China. A cross-sectional study was conducted to assess the prevalence and risk factors of Cryptosporidium infection in children (2 weeks to 10 years old) who were hospitalized for diarrhea. Cryptosporidium oocysts were detected using direct immunfluorescent assay and species were determined by sequencing a fragment (~800 bp) of the 18S rRNA gene. A questionnaire contains host, sociodemographic, family, hygiene, diet, zoonotic, and environmental risk factors was administered to patients to identify key factors associated with infections. The observed Cryptosporidium prevalence was 6.9% and the true prevalence was estimated to be 9.0%. Cryptosporidium infection was similar between male (7.4%) and female (6.1%) children and negatively associated with age (i.e., infection was more likely in younger children). Infections in children were significantly associated with family members’ diarrhea within past one month. Infection in children in suburban hospitals (7.8%) was significantly higher than that in urban hospitals (2.1%). The overall prevalence of Cryptosporidium in rainy season was significantly higher than that in non-rainy seasons. DNA sequences of the 18S rRNA gene from infected children were 99.12% to 100% identical to sequences in the GenBank of C. parvum isolates from humans and animals. Future works should determine the sources of zoonotic Cryptosporidium and routes of waterborne exposure in the rainy season in this region.