The fourth semi-final took place on 27 February 2016 at the Gavlerinken Arena in Gävle, hosted by Gina Dirawi and Sarah Dawn Finer. "Youniverse" performed by Molly Sandén and "If I Were Sorry" performed by Frans qualified directly to the final, while "Håll om mig hårt" performed by Panetoz and "Rollercoaster" performed by Dolly Style advanced to the Second Chance round. A total of 4,592,313 votes were cast by the viewers during the show with a total of 628,870 SEK collected for Radiohjälpen.

In addition to the performances of the competing entries, Dirawi and Finer opened the show with a cover of Guy Sebastian's 2015 Australian Eurovision entry "Tonight Again" titled "Du och jag igen" (English: You and I again), while the interval act featured a performance by Dirawi, Finer and Jon Henrik Fjällgren titled "Hela Sveriges sång" (English: All of Sweden's song). Helena Bergström, who hosted Melodifestivalen 2012 together with Dirawi and Finer, reprised her portrayals of Lasse and Marianne—characters that were part of the interval acts for the 2012 competition. Recurring interval acts such as Jonas Gardell's schlager school and dramatic readings of past Melodifestivalen song lyrics by Swedish actors were also part of the program; Lena Endre performed a dramatic reading of Linda Bengtzing's Melodifestivalen 2006 entry "Jag ljuger så bra".