Abstract: The Xiangjiang River is the largest river in Hunan Province and undertakes multiple water supply functions for domestic life, agriculture, and industry. However, in recent years, the issue of heavy metal pollution in the Xiangjiang River has become increasingly prominent due to industrial development and anthropogenic activities. To comprehensively assess the contamination levels of heavy metals in fish from the main stream of the Xiangjiang River and the potential health risks to the public, we collected samples of 34 common fish species from the main stream of the Xiangjiang River, determined the concentrations of six heavy metal elements copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), manganese (Mn), and arsenic (As) in their muscle tissues, and assessed the pollution level and food safety using the Pollution Index Method and the Target Hazard Quotient (THQ) approach. The results demonstrate that the average concentrations of heavy metals in fish followed the order: Zn>Mn>Cu>Pb>As>Cd. In terms of the maximum enrichment levels, Cu showed the highest concentration in Pelteobagrus fulvidraco, while the highest detected values of Zn, Pb, Cd, Mn, and As were found in Pseudolaubuca sinensis, Squalidus argentatus, Distoechodon tumirostris, Saurogobio dabryi, and Siniperca chuatsi, respectively. The single-factor pollution index evaluation indicates that As pollution was the most severe, followed by Pb, while Cu, Zn, and Cd were within non-polluted levels. Health risk assessment results show that although the individual heavy metal THQ_i values and composite heavy metal THQs values of all fish samples were below 1, the non-essential heavy metal elements (Pb, Cd, As) in some fish exceeded national standard limits. It suggests that long-term consumption of fish from the main stream of the Xiangjiang River may still pose potential health risks to coastal residents due to the accumulation of these non-essential heavy metal elements.