How to make notepad++ start with a blank new file when opened?

Setting is now on the backup page (Settings > Preferences > Backup page).

Uncheck "Remember the current session for next launch" in Settings -> Preferences.

https://stackoverflow.com/a/4675270/2441252

Uncheck the Remember current session for next launch" checkbox inSettings->Preferences->MISC`. (Image from Notepad++ v6.4.5 (Aug. 9, 2013), Unicode.)

As has been noted below. the checkbox has been moved to the Backup tab in more recent versions:

Run it with the launch parameter -nosession

This might be useful f.e if you have opened many documents in previous session and they got lost due to network issue or something else, so Notepad++ produces too much alerts and hangs so you cannot change the parameter in Settings.