The 36-year-old went to the World Cup in 1999 and made his RBS 6 Nations debut against England in 2000 - filling the boots of former Italy skipper Massimo Cuttitta.
Lo Cicero won his 100th cap in this year's competition against Scotland in this year's tournament, becoming their all-time record appearance holder in the last game with England, and returns to the starting line-up for his international swansong.
Contracted to Racing Metro in France's Top 14, Lo Cicero will hang up his boots at the end of the season certain Italy's next generation are ready to take over.
"I'm 36, I would have liked to play at a fifth World Cup in 2015, but I will be 39 when the team goes to England and it's time to leave room for the youngsters, who are not lacking," he said.
"It will be my final game for the national team. At the end of the of the season I will stop playing but I'll keep training and be free for two years if any team needs me as a medical joker.
"But after so many battles, the time was right to say stop. For Italy I have had everything, I've had 14 unforgettable years, I want to thank all the coaches and the teammates who have shared on my path with the national team."