For Spanish speakers trying to learn English, is it hard for them to learn the difference between "at", "in", and "on"?

Answer 1

Prepositions in general are hard to learn in any new language, because their uses tends to be less concrete than general nouns. As with all aspects of the language, but especially with prepositions, one needs to learn how they are used rather than what they mean.

To get back to your question, yes, Spanish speakers learning English often have trouble with at, on, and in.

Answer 2

It can be very difficult to learn the difference. Because the Spanish word "en" can be used for all three of these English words, it becomes a struggle.