Lacson originally planned to run for president in the 2016 election. However, due to low ratings in most pre-election presidential surveys, he decided to run for a senate seat as an independent candidate in the 2016 Philippine general election. He was a guest candidate in the senatorial slates of presidential candidates Jejomar Binay (UNA) and Mar Roxas (LP). He was initially listed in Senator Grace Poe's senatorial line-up, but he was eventually replaced by Edu Manzano. He was also listed in Rodrigo Duterte's (PDP–Laban) senatorial slate. However, on February 15, 2016, the Duterte-Cayetano tandem dropped their entire senatorial line-up.