The Madeirans currently sit at the foot of Group D with only two points from four games after home draws with both the Magpies and French side Bordeaux.
Anything less than three points at St James' Park would end their hopes of progressing and club president Carlos Pereira admits they will have their work cut out against the Barclays Premier League side.
He told www.ojogo.pt: "We recognise that it will be difficult, given that Newcastle have a much higher budget than ours, but I think the Portuguese Cup game against Aguiar da Beira marked the end of our bad run.
"But these games often awaken players, although we know only with a win will it still be possible to progress to the next stage of the Europa League."
The 3-0 cup victory over fourth tier outfit Aguiar da Beira at the weekend came as a welcome boost for Pedro Martins' men after a poor run of results.
Of the nine Portuguese League and European fixtures Maritimo have played since Newcastle's visit to the Estadio dos Barreiros on September 20, they have won just one and lost six.
They headed for England without injured duo Olberdam Serra and Heldon Ramos, but with Ricardo Ferreira, Briguel, Valentin Roberge, Rafael Miranda, Joao Luiz and return to Leocisio Sami all returning after being rested.
Newcastle captain Fabricio Coloccini, midfielder Jonas Gutierrez and striker Papiss Cisse will be available after suspension, injury and FIFA-imposed ineligibility respectively, but midfielder Cheick Tiote is banned and usual partner Yohan Cabaye is facing a spell on the sidelines as he prepares to undergo groin surgery.
Magpies boss Alan Pardew said: "We have lost two home games (in succession) and that's not acceptable for us.
"We need to make sure we win tomorrow [Thursday], and it would also give us qualification, so it's a big night for us."