It’s not nonsensical. It’s an assertion that can be made sense of with a little effort.
Consider the user interface analogy. On your desktop there is a mouse pointer with which you can drag a file from here to there. In the underlying computer which executes the actions which are represented by this interface, there is nothing that resembles a pointer, a dragging action, or a file. That the interface associates certain activity in the hardware with certain things that appear on the desktop is a useful convention for us, but it is not one that was designed to give us an accurate notion of what is taking place inside the machine. Hoffman suggests that the same thing is true of the interface-reality we perceive and the real-reality underneath. The interface-reality was “designed” by natural selection to be a useful convention for us as we interact with the real-reality which is not apparent to us.
We taboo resemblance all the time for things that refer to other things: Words, for example. The word “mouse” does not resemble a mouse, but we can usefully use the word as a reference. Words that resemble their references are a peculiar and remarkable tiny category (onomatopoeia) that are the exception to the rule.
If you thought your computer interface were an accurate picture of what is going on inside the computer, you might indeed go looking for a microscopic pointer somewhere in the wires. It’s because you don’t think this that you know to look for correspondences and representations instead. Hoffman’s point is that we don’t tend to do this with things like space, time, matter, etc.: we think those things in our interface-with-reality correspond to the same sorts of things in reality-under-the-hood (space, time, matter, etc.). He believes we’re mistaken.