Learn French: Il connaît le guide, mais il ne sait pas comment il s'appelle. - He knows the guide, but he does not know what his name is.

This is the core difference between connaître and savoir. We use connaître (here, connaît) because it is followed directly by a noun, le guide (a person). It means being acquainted with someone or something. We use savoir (here, sait) because it is followed by a question word, comment, which introduces a fact or a piece of information.

Could I say Il sait le guide if he knows him really well?

No, you can never use savoir directly with a person. Savoir is strictly for knowing facts, knowing information, or knowing how to do something. To say you know a person, a place, or a specific thing, you must always use connaître.

The English translation says "what his name is", so why does the French use comment (how)?

In French, to talk about someone's name, we use the reflexive verb s'appeler (literally "to call oneself"). So, comment il s'appelle literally translates to "how he calls himself". French does not use words like quoi (what) or nom (name) in this standard phrasing.

There are three ils in this sentence. How do we tell who they refer to?