Two children are thought to have been onboard the aircraft, which was reported overdue from a tour of the Na Pali Coast on Thursday evening.
A search for possible survivors is now underway, although the US Coast Guard said steep terrain, low visibility and choppy seas had complicated the mission.
The tour company, identified as Safari Helicopters, contacted the coast guard at around 6pm to say its aircraft was about 30 minutes overdue, authorities said.
The Eurocopter AS350 lifted off from the town of Lihue, on the other side of the island, a US Federal Aviation Administration spokesperson said.
The last known contact with the aircraft came at roughly 4:40pm, police said, when the pilot relayed that the tour was leaving the Waimea Canyon area.
The helicopter has an emergency electronic locator, but no signals were received. After the alarm was raised, a US navy helicopter was sent to assist the coast guard.
Local fire officials planned to conduct their own search, while commercial helicopter companies and crews on all-terrain vehicles were also being deployed.
The Na Pali Coast is one of the most dramatic and sought-after destinations in Hawaii, and is a mainly uninhabited state park renowned for towering mountains, thick with jungle canopies and cut by deep ravines and vast waterfalls.
Hawaii Department of Land and Natural Resources spokesman Dan Dennison, who has spent years visiting and photographing the area, said winter brings more rain and turbulent seas.
“During the winter, flash floods frequently close the trail out of safety concerns,” he said. “It has numerous streams that can rise very fast.”
The weather is the primary challenge to any search-and-rescue operation in the area, Mr Dennison said.
“You can have very low ceilings. You can have fog and cloud banks that move in very quickly. You can have heavy rain [and strong winds that] make flying difficult if not impossible at times,” he said.
The shoreline has beaches that could potentially serve as emergency landing zones, but they are “few and far between”, with those that exist providing little space for a landing, Mr Dennison said.
But finding a safe place to land in the interior wilderness would be much more difficult, he said, and searching those areas from the air is also a challenge.
“It’s such a vast area with so many ins and outs and pockets of vegetation,” he said. “It’s just really hard to see from the air through the heavy canopy.”
A person who answered the phone at a number listed for Safari Helicopters declined to comment and hung up.
Additional reporting by AP