You can try - I certainly did - but it's inferior, in nearly every way: performance most of all, usability, interfacing with the host OS, availability of libraries, APIs, interactive documentation, discoverability, customization..
The fact that Emacs has been in use (for decades) as a tool aimed at primarily solving everyday problems, means that it's been optimized for practicality to a ridiculous extent. That's not the case with Squeak, since it still has a very strong academic/research focus and a much smaller userbase than Emacs.
That's not to say that Squeak is useless, I'm a hardcore Emacs user and I do use Squeak too, but it's nowhere near as practical. It does however offer by far the best environment to experiment with Smalltalk and image-based development.
On the other hand, I don't recommend Pharo, as I found it even less practical than Squeak with frequent braking changes and a -seemingly- complete lack of focus that has pulled the project in widely different directions over the years. At least, Squeak is cohesive and hasn't broken with Alan Kay's vision.