Human parainfluenza viruses (HPIV) are common viral pathogens in acute respiratory infection (ARI). We aimed to describe the epidemiological and molecular characteristics of HPIV from ARI patients. This cross-sectional study was conducted using respiratory samples from 9,696 ARI patients between 2016 and 2020 in southern China. All samples were analyzed by quantitative real-time polymerase chain reaction to determine the presence of HPIV and other common respiratory viruses. Descriptive statistics were performed to determine the temporal and population distribution of HPIV. The full-length hemagglutinin-neuraminidase (HN) gene of HPIV3-positive samples was sequenced for phylogenetic analysis. A total of 577 (6.0%) patients tested positive for HPIV, with HPIV3 being the predominant serotype, accounting for 46.8% of cases. Notably, 66.0% of these HPIV-positive cases were children aged 0-2 years. The prevalence of HPIV infections showed a decreased trend and altered peak during 2016-2020. Cough, fever, sputum production, and rhinorrhea were common respiratory symptoms in HPIV-positive patients. The majority of cases had pneumonia (63.4%). Human rhinovirus (HRV) and human coronavirus (HCoV) were the most common coinfection viruses in HPIV-positive cases, with proportions of 20.1% and 14.4%, respectively. Phylogenetic analysis revealed that the predominant lineage of HPIV3 was C3f (86.0%), followed by lineage C3a (8.0%), C3d (4.0%), and C3b (2.0%). These findings help to better understand the epidemiology of HPIV, and improve public health strategies to prevent and control HPIV infections in southern China.