Innoko National Wildlife Refuge supports a healthy moose population. With no roads anywhere near the refuge, hunters ride in float-equipped airplanes and land on refuge lakes. Guided hunting is popular, but many hunters choose to go on their own. Unguided hunters are dropped off on the upper reaches of the Innoko River or one of the smaller rivers that flow into it. The float trip takes from a week to 10 days. Some hunters prefer a boat with a small motor for better access to tributaries in order to check prime moose locations multiple times. Moose are usually found along the riverbanks or in nearby meadows. Hunters could also encounter black bears, wolves and wolverines, and some bring a shotgun to pursue the refuge's waterfowl species.
Most of the hunters that visit the refuge, primarily in search of moose or waterfowl, are residents of neighboring villages (Grayling, Anvik, Shageluk, and Holy Cross) or the nearby towns (Galena, McGrath and Bethel). Caribou, black bear and other furbearers are also pursued in season. Furbearers are also taken through trapping, including wolf, wolverine, marten, beaver and lynx.