Newcastle make five changes - all in the pack - following last weekend's 43-21 Premiership defeat at London Irish.
Open-side flanker Will Welch is back as captain along with number eight Carl Fearns, lock Marco Fuser and props Kyle Cooper and Mark Tampin.
Worcester return to Newcastle just a fortnight after their weather-delayed two nights on Tyneside.
Wing Alex Hearle returns and Will Chudley starts at scrum-half but Rory Sutherland and Matt Garvey are out.
Scotland prop Sutherland has a dead leg while lock Garvey took a blow to the head in last weekend's narrow 32-31 Premiership win over Wasps.
Chudley takes over in the number nine jersey after Gareth Simpson aggravated a rib injury,
But out-of-favour former England wing Chris Ashton is again not considered for selection, as has been the case all season, with his absence a continued source of media speculation.
These two sides eventually shared a 24-24 Premiership draw on 27 November, a day after Warriors were forced to stop over following an initial postponement caused by Storm Arwen.
Returning Falcons skipper Welch is one of seven Falcons starters who started the league game, while 16 of Worcester's matchday 23 are involved again on European Challenge Cup duty
Newcastle have advised supporters they will not be asking for Covid passports for Friday's match, following the government's announcement that fans will need to show proof of double vaccination or a negative test to attend sporting events with crowds of more than 10,000 people in England under new Covid-19 rules from 15 December.
A Falcons statement said mask-wearing is not required when outdoors watching the match, indoors in a hospitality environment, or eating and drinking, but for safety they advise that face coverings are worn whilst entering and moving around the stadium.
Newcastle director of rugby Dean Richards:
"We've got a lot of boys carrying injuries or niggles. Aside from that, we're putting out the strongest team available.
"Playing Worcester a fortnight ago is useful in many ways, and gives us a good understanding of what they're about.
"If I was being particularly blunt about it we were very disappointed with the performance that day, to score four tries and only get three points. We weren't happy with conceding the three tries in the manner we did. On top of that, we then conceded a shed-load of points at London Irish last weekend."
Worcester head coach Jonathan Thomas:
"We will certainly be taking this competition seriously. If you want to be a top player and a top-six team, you have to get used to playing every week and having a mindset where you go, you go, you go.
"If we have the vision to being a top-six Premiership club in the future and playing in the Champions Cup, we have to get used to backing up performances and backing up results.
"We can't have the mindset that it's the Challenge Cup so we will have a down week. That's not how top players and top teams operate. We definitely want to go into this competition with the mindset to keep the positive momentum from the last few weeks going."
Newcastle: Brown; Penny, Wright, Burrell, Radwan; Haydon-Wood, Schreuder; Cooper, McGuigan, Tampin, Fuser, Robinson, Chick, Welch (capt), Fearns.
Replacements: Smith, Brocklebank, Mulipola, Peterson, Graham, Nordli-Kelemeti, Hodgson, Lindsay-Hague.
Worcester: Shillcock; Hearle, O Morris, Venter (co-capt), Van der Merwe; Searle, Chudley; Waller, Annett, Tyack, Batley, A Kitchener, Hatherell, Hill (co-capt), Vailanu.
Replacements: Baldwin, Owen, Judge, Kvesic, Lewis, Wynn, Smith, Doel.
Referee: Frank Murphy (Ireland).