Yes, as Alex has said. It is used especially when the person is just about to do something in the near future. For example: "When John has that smirk on his face, you know that he is up to no good." That means that when you see that particular type of smile on his face, it is because he has some evil plan in mind to do some nasty thing. Think also about the expression "What are you up to?" It means what are you doing now or in the next short while? (This one is not a negative expression, it carries no negative meaning.) So, to use both the expressions: One could ask... "Why is John smirking like that, what is he thinking, or what is he up to?" The answer could be... "He is up to no good!" Note, both these expressions are slang.

To be "up to no good" is to be causing trouble or making mischief. If someone's up to no good, they're a troublemaker.