Take tram 2 in the direction Nouveau Bassin and get off at the stop Lefabvre. There change to a bus 22 in the direction Rixheim/CentreNautique (goes every half an hour, better check it) and get off at the stop Berne or CentreCommercial, by the Carrefour shopping centre. Walk 5 minutes north and you will find a bridge with the entrances to the motorway in both directions. Going towards Dijon, better choose the spot on the left. Going east Mirto got a ride from here directly to Prague.
If you are going west, accept a lift at least to the big service station Porte d'Alsace, where it's easy to get a long-distance lift. Don't get off at the first péage west of Mulhouse, as the staff don't tolerate hitchhikers and there are many police there.