The Nikkei 225 was down 0.96% at 19,115.48 in early trade, while the dollar weakened against the yen.
A stronger yen hurts Japan's big exporters as it makes their products more expensive to buy overseas.
Australian stocks were down in early trade despite positive job numbers.
The country's jobless rate came in at 5.8% in November, down from 5.9% the month before -  the lowest reading since early last year.
The Australian Bureau of Statistics also said 71,400 new jobs were created for the month, against forecasts for a fall of 10,000. The Australian dollar rose more than 1% against the US dollar on the news.
Sydney's S&P/ASX 200 was down 1.64% however at 4,998.10 points, with the country's big lenders dragging on the benchmark index.
Westpac and Commonwealth Bank were both down close to 2.5%, ANZ was down 2.35%, while National Australia Bank was the biggest loser, down more than 3%.
In China, investor sentiment was mixed, with the Shanghai Composite index up 0.41% at 3,486.91 , while Hong Kong's Hang Seng was flat, up just 0.05% at 21,813.12.
Korea's benchmark Kospi index was flat, down 0.07% at 1,946.28.
Japan's benchmark Nikkei index was one of several stock markets to fall across Asia on Thursday, as the country's big exporters were hurt by a stronger yen.