On the one hand, taking in everything you can tell about a situation and making your best judgement is part of the pragmatics of human conversation. When someone tells you "that's just what we needed!" a small change in tone of voice can shift the polarity entirely, indicating the opposite of the plain reading via sarcasm. On the other hand, several people have told me that as kids they hated being tickled but would involuntarily smile and laugh while objecting, which the adults around them misunderstood. In general, ignoring a 'no' seems pretty risky, especially in cases where we know some people have misleading involuntary reactions.
Instead, when our kids would do the no-with-giggle I would respond the same way as if they'd given a fully serious 'no'. They were initially confused by this, and would sometimes repeat the no-with-giggle more emphatically. I'd ask again if they wanted tickles, and only tickle them if they said 'yes', trying to teach them that they needed to give clear signals. Over time their no-with-giggles responses petered out, and they started consistently saying 'yes' or 'no' when I offered tickles.
This was very surprising to me: I wouldn't have expected the mixed signals response to come so naturally, and need explicit practice to learn to suppress.