In 2020, at the age of 16, Hsu starred in Chinese musical theatre film The Day We Lit Up The Sky. Her debut performance earned her the Best Newcomer Award at the 2021 Tokyo International Film Festival. In 2025, Natalie was nominated in the Best Actress category at the Hong Kong Film Awards and Hong Kong Film Critics Society for her lead role in Last Song For You; she was also awarded the Screen Daily International Rising Star award at the New York Asian Film Festival. In 2026, she was nominated again for Best Actress at the Hong Kong Film Awards following performance in My First of May.