This is the big show down on the Defias leader, Edwin VanCleef, and you get it after completing a whole series of minor quests ending with The Defias Brotherhood VI. Speak to Gryan Stoutmantle who will say:

There is one task left for you to complete. Edwin VanCleef must be assassinated. While it saddens me to condemn any man to a death sentence, it is for the greater good of the people of Westfall that VanCleef is laid to rest once and for all. Bring me the villain?s head once the deed is done.

Kill Edwin VanCleef
Bring his head to Gryan Stoutmantle

To complete this quest you should get a group preferably of five people in their mid twenties, although it can be done close to twenty if you?re very careful. once you got your posse together, head into the Deadmines below Moonbrook. You will now have to fight your way through the entire length of this dungeon, fighting elite opponents from level 15-20. You might want to read the Deadmines instance guide for more detailed information.

At the end of the Deadmines you will find yourself in a large cave with a ship in the middle. Move careful through the Defias Pirates (level 19-20 Elite) and Defias Squallshapers (level 19-20 Elite) until you reach the ramp leading up to the ship itself. Be very careful here! Atop the ledge is a tauren named Mr. Smite (level 20 Elite) and two invisible Blackguards (level 19-20 Elite) which will attack once you attack the first mate. Some good planning is required here, so choose your tactics well.

Clearing your way through the ship will bring you to another difficult spot as you reach the upper deck guarded by Captain Greenskin (level 20 Elite) and several pirates. They patrol the deck, so make sure you are ready for them when they pass you, and clear them away before taking on the main guy. Edwin VanCleef (level 21 Elite) is waiting in the cabin close to where you advance. With him are two invisible Blackguards (level 19-20 Elite) so you?re up for a tough fight here unless you?re prepared with freezing traps, area damage or polymorph. Kill the main guy next, loot his head and return to Stoutmantle who will say:

Your bravery is remarkable. The People?s Militia thanks you for your service to the people of Westfall. With VanCleef dead, this marks the beginning of the end for the Defias Brotherhood. Hopefully some day soon peace will once again grace the plains of this fair land.

While looting Edwin VanCleef you will also find an Unsent Letter, which will begin a quest associated with The Stockades, so make sure to keep that one in a safe spot until you?re ready.

Skylerx adds:
Start at Defias hideout and enter up into the deadmines where you go through many caves and fight miners and many other types of enemies. Then you enter the instance where you take on 3 head guys .When you get to shredder it is best to get a hunter to lure them 1 by 1 or 2 by 2. Try and get all the little ones before you attack Shredder and there is a chest usually in far corner where you enter. When you go to goblin foundry be very careful because it is pretty hard. When you get to Smite get the highest level guy to take on Smite while two others take on each rogue. Best way to get VanCleef is to lure him out or either get a rogue to go in there are two rogues and VanCleef inside and after you kill VanCleef loot the head of VanCleef and sometines the Cruel barb drops which is a great sword. Then you have to work your way to Cookie then your way out. I recommend you have at least level 20+ people and a healer and a warrior so that they can tank. After you return back to sentinel hill you will get Tunic of westfall or 2 other nice things there all blue. Enjoy and becare. Safe Journeys.