For detailed information see the official docs.
Configure your nextcloud instance to use the gateway:
root@nextcloud:~# sudo -u www-data -H php /var/www/nextcloud/occ twofactorauth:gateway:configure signal
Please enter the URL of the Signal gateway (leave blank to use default): https://signal-gateway.example.com/
Using https://signal-gateway.example.com/.
Now you can use setup for your user in the security settings section.