The fire was at a building in the 5400-block of South Justine Street in the city's Back of the Yards neighborhood about 11:30 a.m.
CFD said three firefighters were taken to hospitals in serious condition and one in good condition.
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It's not clear what led up to the injuries.
"The challenge was the amount of fire, the heavy amount of fire, and just the weather. You know, it's still summertime, even though it's a little bit cooler than it was a couple weeks ago. We're still talking 80 degrees," Chicago Fire Deputy Chief Chris Serb said. "There were no indications when they pulled up on the scene that this building was in fact vacant. It turned out that it was in fact vacant, but there were no indications."
CFD said the fire has been put out.
Some residents heard the commotion and ran outside.
"I just grabbed my baby and ran out. I just ran out. It was horrible. All you see was smoke everywhere. Firefighters running to get some water, trying to put the fire out, it was just, it was too much going at the same time," neighbor Erika Echevarria said. "The flames, I'm scared. I'm like I'm scared even for the firefighters because they're always putting their life under risk."
Kim Bradley shared video.
She and other neighbors had been concerned because they say the home had been vacant for years.
"Before this happened, I actually contacted the city to tear this building down, said it was a fire hazard. They claimed they came out, looked at it, but nothing happened. So, what do you think of that? I think something should happen because I always thought about this building being so close to ours that our building could catch fire," Bradley said.