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You can password-protect a zip, and therefore also an epub. It would probably no longer be a spec-compliant epub and few applications (if any) would recognize and open it as an epub.
But before you embark into creating or modifying an app to read those files, note that anyone with the password to open the book and read it would also have the password to open the book and modify it.
If your concern is not so much preventing modification, but being able to tell whether the book is the original or a modified copy, you can always publish some checksum like md5 or sha-256. That way your readers could verify that their copy is identical to the one approved by you.
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