What do you think ________ troubles him most from time to time?

A.it is that

B.that is

C.which is

D.it is

答案及解析： A

解析：

do you think在这里是插入语，这是一句强调句，Do you think it is sth that troubles him most from time to time．而这里的sth正是trouble的主语，也是强调句的被强调部分，因此用what提问。