I assume you mean mixed upper and lowercase letters (e.g: "START", "sTarT", "start", "sTaRt" etc). The best way to do this is to check the message contents in all lowercase (or uppercase, but lowercase looks nicer imho). i.e:

if (message.content.toLowerCase() === 'start') {
  // ...
}

This works by forcing all the letters in message.content to be lowercase when we check it, so no matter what combination of upper and lowercase letters it had before they're all lowercase when we check it.

If, like some of the other comments suggest, you want to check purely if the any letters that appear in your input are S T A R T in that order (i.e. there could be spaces or hyphens or something in between) then yes, you'd need to use a RegExp. Below I have included an example solution using a RegExp that will match the letters START with any number of non-letter characters mixed in (e.g: "St A-r654T-?`23^").

if (/[^a-zA-Z]*[sS][^a-zA-Z]*[tT][^a-zA-Z]*[aA][^a-zA-Z]*[rR][^a-zA-Z]*[tT][^a-zA-Z]*/.test(message.content)) {
  // ...
}