Six astronauts and scientists participating in the NASA Extreme Environment Mission Operations, or NEEMO, program left the Aquarius Undersea Laboratory after five days.
The start of the 15th NEEMO mission had been delayed by another storm in the area.
NASA said it will not reschedule the simulation, which was slated to last 13 days off the coast of Key Largo. The goals of the mission were to practice operations and test tools being developed for a future planned human mission to an asteroid.
Rina, a surprising late addition to the 2011 Atlantic hurricane season, was headed toward Mexico's Yucatan peninsula but losing strength on Wednesday.
Computer models forecast Rina, the sixth hurricane of the Atlantic season, will weaken into a tropical storm and move over western Cuba, potentially bringing strong winds and heavy rains to southern Florida and the Keys.
Participants in the NEEMO mission included NASA astronaut Shannon Walker, Japan's Takuya Onishi and Canada's David Saint-Jacques and scientists Steven Squyres with Cornell University and James Talacek and Nate Bender with the University of North Carolina at Wilmington.
The NEEMO crew conducted six underwater spacewalks and one day of scientific research. They also used a deep-water submersible to simulate robotic exploration of an asteroid.
"Despite the length, we accomplished a significant amount of research," NASA project manager Bill Todd said in a statement.
The next NEEMO mission is targeted for the summer of 2012. The 400 square-foot lab, which is about the size of a school bus, is anchored to the ocean floor near Key Largo at a depth of about 62 feet.
(Editing by Kevin Gray and Cynthia Osterman)