Huslia lies on the north bank of the Koyukuk River
within the Koyukuk National Wildlife Refuge
. Originally spelled Huslee, Huslia was named after a local stream.
Huslia is an Athabascan village, and most residents are related by birth or marriage. Subsistence is central to the local economy. River transportation is used extensively in the summer, and Huslia is accessible by air year-round. Huslia also has an extensive network of winter trails, and the frozen river acts as an "ice road" to neighboring villages.