From Monday until April 17, anyone with a hunting license who pays for the $26 permit can take them on state-managed lands around the Everglades in South Florida.
Florida officials have taken a more aggressive stance against the invasive species in the past year, creating the python hunting season and issuing broader permits to experts to kill as many as possible.
The state has even held workshops for those inexperienced with pythons on how to identify, stalk and capture the reptiles.
In addition to Burmese, Indian and African rock pythons, hunters can also take green anacondas and Nile monitor lizards.
As for the dead snakes, local tanners say they will pay $5 to $10 per foot.
"It's definitely a hot item. Hermes, Gucci, Prada, all the top manufacturers use python skins," said Brian Wood of All American Gator in Hallandale Beach told CBS News 4 in Miami. "And we have it right in our backyard."
Hunters must report each kill to the wildlife commission.