Sixx was born Frank Carlton Serafino Feranna, Jr. on December 11, 1958 in San Jose, California. He is of Italian ancestry on his father's side. Sixx was partially raised by his single mother, Deana Richards, and by his grandparents after his father left the family. Nikki later moved in with his grandparents after his mother abandoned him.

Launched on February 8, 2010, Sixx Sense with Nikki Sixx broadcasts Monday through Friday from 7 p.m. to midnight local time on rock/alternative music stations. Each night, host Nikki Sixx discusses music and lifestyle topics as he gives listeners a backstage look at the world and mind of a rock star. Sixx was joined by co-host Kerri Kasem, from its first episode until March 28, 2014. On April 2, it was announced that radio personality Jenn Marino would be joining the show in Kasem's place. The show is based in Dallas, Texas in a studio in the Northpark Center.  Starting on May 7, 2012, KEGL in Dallas/Fort Worth, Texas moved the show to mornings, making it the only station to carry the show in the mornings at 6 to 10 AM local time instead of the evening's time slot. The show is customized for the Dallas/Fort Worth listeners for broadcast in the mornings on KEGL. Sixx said that bringing Sixx Sense to mornings "has always been our goal. Who better to start your morning with than a rock star and a hot chick? It's a dream come true to have a morning show on one of America's best rock stations." however, one year later, Sixx Sense returned to Evenings at KEGL. In addition, recent episodes of "Sixx Sense" airs 24/7 on its own iHeartRadio streaming page.  The Side Show with Nikki Sixx is a two-hour original weekend program. Airing Saturday or Sunday between 6 a.m. and midnight local time, Nikki Sixx will air top-charting songs, showcase new and emerging artists, and welcome guests from the worlds of music and entertainment. In October 2017 Sixx announced that he would step down from Sixx Sense on December 31, 2017.

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