Three high-frequency sampling and monitoring experiments were performed at the Lutang and Luowei transects of the Liujiang River entrance and at the southeast exit of the Liuzhou during 2019 for the purpose of assessing physico-chemical variables and human health hazards of water heavy metals in different rainfall processes. There were significant seasonal variations in concentrations of 11 heavy metals and most variables showed higher levels during the dry season. The distribution of heavy metals in the Liuzhou area varied significantly by region. Pollution source analysis indicated distinct seasons of wetness and dryness. The dry season is dominated by anthropogenic activities, while the wet season is dominated by natural processes. The results of hazard quotient (HQ) and carcinogenic risk (CR) analysis showed that the health risk of non-carcinogenic heavy metals in the wet season is slightly higher than that in the dry season. Seasonal changes in carcinogenic risk are the opposite; this is due to the combined influence of natural and human activities on the concentration of heavy metals in the river. Among them, Al was the most important pollutant causing non-carcinogenic, with As being a significant contributor to carcinogenic health risk. Spatially, the downstream Luowei transect has a high health risk in both the dry and rainy seasons, probably due to the fact that the Luowei transect is located within a major industrial area in the study area. There are some input points for industrial effluent discharge in the area. Therefore, high-frequency monitoring is essential to analyze and reduce the heavy metal concentrations in the Liujiang River during dry and wet seasons in order to protect the health of the residents in the area.