I need to communicate the time we need to leave a house in order to catch a train, should I say "We should set out at 18:15" or "We should hit the road at 18:15". Does it have the same meaning? What native speaker prefer?

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    It depends entirely on context. To hit the road is an extremely informal / colloquial usage, that wouldn't always be appropriate anyway. Besides which not everyone would be happy to extend the (highly figurative) sense if the planned journey were to be by train, for example. But note that set out / set off would never be "inappropriate", so if you're not sure of your context, you should definitely stick to that. – FumbleFingers Reinstate Monica Feb 11 '16 at 15:13

set out
set off
hit the road
be on our way
be on the road
get going

are all expressions to say when to start off on a journey and have the same meanings

After one of these expressions, the designated time is given by a time or some other appropriate preposition: at, before, after

We should leave by 10:00
We should be on our way after lunch
We can leave before breakfast
We need to leave just after the show to make our train

Most usual is to use a simple leave

I will leave at 6:00
I'll be gone before you wake up

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