The "Ghostbusters" star had been due to portray disgraced Elizabeth Holmes, the woman who skyrocketed to prominence as one of the youngest self-made billionaires ever in 2014, after claiming scientists at her biotech company Theranos would revolutionise blood testing by using just a pinprick of blood, as opposed to the usual syringe method.
However, her blood-testing machine didn't really work and the results were inaccurate, and in 2018, she and a former Theranos boss were indicted on a string of wire fraud and conspiracy to commit wire fraud charges for falsifying results to consumers.
The show, based on the podcast of the same name, was given a straight-to-series order in 2019, with McKinnon on board as executive producer and star, but now she has exited the project.
According to Deadline, Hulu officials are still planning to move forward with the miniseries, and are currently searching for a replacement, ahead of a planned summer production start.
It's the latest screen project to explore Holmes' story - it was also the subject of the 2020 documentary "The Inventor", directed by Alex Gibney.
Jennifer Lawrence had also previously been linked to the role of Holmes in a planned Adam McKay film called "Bad Blood" although it's unclear if the film, initially announced in 2016, is still in development.
Kate McKinnon is among the "Saturday Night Live" regulars. She also lent her voice to animated series "Nature Cat" and "The Magic School Bus Rides Again".