You can double-team him and hope to neutralize him. Or you can block him one-on-one and start thinking about a good play to call on second-and-12.
That's what his head coach, Georgia Military College's Bert Williams, discovered last fall.
"He gets double-teamed most of the time," Williams said. "When he doesn't, it's obvious because he gets back there in the backfield where he's not supposed to be."
Because of his imposing size and junior college background, McCullers is often compared to former Alabama All-American Terrence Cody, a 6-foot-4, 360-pounder who now plays for the NFL's Baltimore Ravens.
"Because of the junior college background, the guy people mention most often is Mount Cody," Williams said. "Nick Saban (who coached Cody at Alabama) saw Daniel and said, 'Shoot, he runs better than Cody right now.' Of course, I don't know if that was true or just recruiting talk."
"He reminds me of Vince Wilfork and how he collapses the pocket," Williams said. "That reminds me a lot of the way Daniel plays."
Because McCullers weighed 400 pounds as a high school senior, many coaches figured he would never develop the discipline to play college football. Georgia Military's staff decided to gamble on him, however.
"I was referred to him by the coach at another SEC school," Williams recalled. "We were trying to find a couple of linemen to fill our needs. This coach had seen Daniel in a camp and said we ought to look in on him. When you hear his size, you have some concerns. We watched the film, though, and saw he had some skills that were pretty special and decided to try and get him ... which we did."
The gamble paid off in a big way. McCullers recorded 37 stops, nine tackles for loss, two sacks, a fumble recovery, a pass breakup and a blocked kick last fall, despite being double-teamed on almost every down.
"It always takes two (blockers) to try to handle him," Williams said. "If you leave him one on one he's going to penetrate the backfield, whether it's a run or a pass play."
That's probably because, in addition to great size, McCullers has great strength.
"A lot of time tall guys — tall guys his age, in particular — don't have great upper-body strength," Williams said. "But he has great upper-body strength. He benches more than 400 pounds, probably 440 or 450. There comes a time where there's no point trying to break records and tear a pec (pectoral muscle). And he squats well over 600 pounds."
McCullers played nose guard at Georgia Military and projects to do the same at Tennessee. His coach thinks the massive young prospect could play defensive tackle, too.
"Yeah, he could play the 3 technique," Williams said. "It's just a matter of what you're trying to get out of him. If you put him out there (at tackle) and have a guard try to handle him one on one, that's going to be a pretty tough time for that guard."
Most nose guards have fireplug builds and a low center of gravity that makes them difficult to dislodge. McCullers' height makes keeping blockers off his legs a lot more difficult.
"That's something he has to work on ... pad level," Williams conceded. "He can do it. He's gotten a lot better over time. But that's something he'll have to continue to work on."
At 380 pounds, McCullers is virtually immovable on running plays. Naturally, that is the strength of his game.
"He's exceptional against the run," Williams said. "It's very difficult to run anything inside the tackles — any of the zone schemes — because he redirects very well. A lot times people try to cut behind him but he's pretty quick in that box; most running backs, if he gets a hand on 'em, he's going to bring 'em down."
Although he'll never be a speed rusher, McCullers is effective against the pass, as well.
"People talk about speed," Williams said, "but if that pocket's going back three or four yards, that quarterback is going to have to move laterally toward the ends or step up into the pocket and right into Daniel.
"He can disrupt the passing game even if he doesn't get the sack. I think his ability to affect the pocket is under-appreciated. I think he'll give the Vols a little more in that area than they think."
McCullers will sign with the Vols on Wednesday, finish his studies at Georgia Military, then show up for Tennessee's preseason drills in August. Williams believes Big Orange fans are going to love this big behemoth.
"I think he'll get better every day from the time he sets foot on Tennessee's campus until the time he finishes," the coach said. "He responds well to coaching and still has a lot of room to grow and improve."
A lot of room to improve, at least.