Cardiff Blues, Gloucester Rugby, Northampton Saints and Saracens are all in the hunt for silverware, which offers a Heineken Cup place to an English winner.
LV= Cup Tournament Director Terry Burwell said: "Sixways is a first class stadium with excellent facilities and we are delighted to take the LV= Cup final there as the RFU has done with some of England's Under 20 fixtures.
"All four semi finalists have fervent support and we believe that March 21 will be a great day out for whichever two clubs get there. The LV= Cup has given us some spectacular rugby this season, as well as the chance to see some exciting young English players, and with the semi-finals just a week earlier there will be a great momentum towards the final."
Worcester Warriors General Manager Charlie Little added: "It is a great honour and huge privilege for Worcester Warriors to be chosen to host the LV=Cup final in 2010.
"This is recognition for the recent development of Sixways Stadium and our facilities as we have strived to create what we believe is one of the best rugby venues in the country. That effort and vision has previously seen us host England representative matches and we are now delighted to be able to host a major domestic cup final for the first time in our history.
"We would like to wish the best of luck to all the semi-finalists and look forward to welcoming the teams and supporters for a memorable LV=Cup final in March."
Tickets will be available from the finalists and Worcester Warriors.