It is certainly plausible that Hughes could win in the Electoral College while losing the popular vote (all it takes is a switch of a few thousand votes in California) but that in itself wouldn't lead to a disputed election (let alone to an Electoral Commission, which was an event unique to 1876). After all, Harrison had won the electoral vote in 1888 while losing the popular vote, and nobody seriously questioned the legitimacy of his election.
If Hughes wins California and the electoral vote, unless there is some strong evidence of fraud, that will be final.
One qualification to this: Democrats did allege that Republicans were luring southern African Americans to Indiana, Illinois, and Ohio to vote--allegedly in violation of the states' residency requirements.
https://www.alternatehistory.com/forum/threads/the-disputed-presidential-election-of-1916.449868/ But as it turned out, there was no plausible basis for challenging the results in those states. Ohio went Democratic, and Hughes' margins in Illinois and Indiana were too large to be explained by any supposed influx of illegal black voters--of which there was no evidence in any event.