I know how to set it in my /etc/profile and in my environment variables.

But what if I want to set it during a script? Is it import os, sys? How do I do it?

You don’t set PYTHONPATH, you add entries to sys.path. It’s a list of directories that should be searched for Python packages, so you can just append your directories to that list.

sys.path.append('/path/to/whatever')

In fact, sys.path is initialized by splitting the value of PYTHONPATH on the path separator character (: on Linux-like systems, ; on Windows).

You can also add directories using site.addsitedir, and that method will also take into account .pth files existing within the directories you pass. (That would not be the case with directories you specify in PYTHONPATH.)

You can get and set environment variables via os.environ:

import os
user_home = os.environ["HOME"]

os.environ["PYTHONPATH"] = "..."

But since your interpreter is already running, this will have no effect. You’re better off using

import sys
sys.path.append("...")

which is the array that your PYTHONPATH will be transformed into on interpreter startup.

If you put sys.path.append('dir/to/path') without check it is already added, you could generate a long list in sys.path. For that, I recommend this:

import sys
import os # if you want this directory

try:
    sys.path.index('/dir/path') # Or os.getcwd() for this directory
except ValueError:
    sys.path.append('/dir/path') # Or os.getcwd() for this directory

PYTHONPATH ends up in sys.path, which you can modify at runtime.

import sys
sys.path += ["whatever"]

you can set PYTHONPATH, by os.environ['PATHPYTHON']=/some/path, then you need to call os.system('python') to restart the python shell to make the newly added path effective.

I linux this works too:

import sys
sys.path.extend(["/path/to/dotpy/file/"])