First decide which races you're playing with, then select the number of players, and finally decide how many races you want each player to be able to choose from. For your first game, choose the races marked with *. Races marked with ^ are tricky to play; new players may want to avoid them.
The option for determining the Speaker supports an optional house rule, used by some groups, where the Speaker gets one fewer racial choice (e.g., "everyone gets two races to choose from, except the Speaker who only gets one"). Do not choose this option if you're playing by the standard rules.
See our Twilight Imperium 4 wiki for more resources.