You know someone's guilty of something when...

They plead the Fifth Amendment.  If you're innocent you can't plead the Fifth because if you've done nothing wrong you can't honestly invoke the Fifth Amendment.  Here's what the Fifth Amendment says

"No person shall be held to answer for a capital, or otherwise infamous crime, unless on a presentment or indictment of a Grand Jury, except in cases arising in the land or naval forces, or in the Militia, when in actual service in time of War or public danger; nor shall any person be subject for the same offense to be twice put in jeopardy of life or limb; nor shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law; nor shall private property be taken for public use, without just compensation"

If you've done nothing criminal you can't be a witness against yourself only a witness for yourself. While it is true that one can construct hypothetical situations where someone didn't do anything wrong but it might appear that way but those situations are probably more likely in a novel than in real life.