Last year proved a stellar one for the German, who rose to the top of the WTA rankings with victories at the Australian and US Opens, as well claiming a runner-up finish at Wimbledon.
But her start to this season has been a different story, Kerber's Australian Open defence ended in the fourth round by Coco Vandeweghe and, in her first match since that disappointment, she suffered defeat in three sets to Kasatkina in Doha.
Kerber had lost to the Russian in Sydney in January and Kasatkina proved a problematic opponent once more, prevailing 6-4 0-6 6-4.
As the top seed, Kerber enjoyed a first-round bye and looked to have rediscovered some form in bagelling Kasatkina to get back on level terms, but she fell 4-0 behind in the decider and could not recover.
With rain playing havoc with the schedule throughout the week in Doha, second-round matches were still being played on Friday (AEDT).
Lauren Davis, Sam Stosur and Karolina Pliskova all joined Kasatkina in the quarter-finals, which are due to be completed later the same day.