Runaway league leaders Leinster have already guaranteed top spot and the first of the home semi-finals, leaving Munster, Glasgow, Ulster and the Scarlets battling it out with the Ospreys for the second sought-after tie.
The Ospreys host the Dragons at the Liberty Stadium tomorrow before travelling to Aironi on May 5 and Humphreys hopes his men can remain on track for a record-breaking fourth Celtic Rugby crown.
"We are in a good position because we know that if we win the next two games then we are in the play-offs with home advantage," said Humphreys, whose men have lost just once in the PRO12 at the Liberty this season.
"Getting a home semi-final is vitally important, especially with our home record.
"We had that in the first year of the play-offs when we played Glasgow and it was a big advantage. The next time we went out to Munster for a semi-final and it was a difficult proposition."
In order to finish in second spot, the Ospreys desperately need a win over the Dragons in Swansea but Humphreys admits achieving that aim will be far from straight forward.
Darren Edwards' side may have lost their last two games at home to struggling Treviso and Connacht but Humphreys is expecting a tough test thanks to the presence of Wales stars Danny Lydiate, Luke Charteris and Toby Faletau.
"It's sometimes hard to understand the Dragons' position in the table given the players they have in their squad," added Humphreys.
"The likes of Toby Faletau, Dan Lydiate and Luke Charteris are world-class players and backs like Aled Brew are very dangerous. These are all guys who can change a game.
"The Dragons always seem to do well against us so we're under no illusions how tough it's going to be. They will be a different proposition to the Blues last week."