Born in Turin, De Filippi began his career in medicine, specializing in experimental surgery and physiological chemistry. He taught at the Universities of Bologna and Genoa. A keen mountaineer, he had already completed many ascents when, in 1897, he was invited by the Duke of Abruzzi to join an expedition in Alaska. Six years later, he crossed the Caucasus and traveled in Turkestan. In 1909, he accompanied the Duke of Abruzzi once again, this time in an extensive exploration of the Karakorum. In 1913-1914, he organized and led an Italian scientific and geographic expedition to Baltistan, Ladakh, and Chinese Turkestan (Sin-Kiang).