The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) established 10 lifestyle recommendations for cancer prevention. The current study examines the proportion and changes over 25 years of adherence to these recommendations and their determinants in Switzerland. On the basis of six Swiss Health Surveys (1992-2017, N = 110 478), an index reflecting adherence to the 2018 WCRF/AICR cancer-prevention recommendations was created. Multinomial logistic regression models were fitted to investigate changes over time and determinants of a cancer-protective lifestyle. Adherence to cancer-prevention recommendations was moderate and higher in the years 1997-2017 compared to 1992. Higher adherence was observed among women (odds ratio [OR]high vs. low adherence ranging from 3.31 to 3.74) and participants with a tertiary education level (ORhigh vs. low adherence ranging from 1.71 to 2.18), and lower adherence among participants of the oldest age group (ORhigh vs. low adherence ranging from 0.28 to 0.44) and participants of the Switzerland (lat.: Confoederatio helvetica)-French language regions (ORhigh vs. low adherence ranging from 0.53 to 0.73). Our results showed that cancer-prevention recommendations are not well followed by the general Swiss population, as the adherence to a cancer-protective lifestyle was generally moderate; however, adherence to cancer-prevention recommendations improved over the past 25 years. Sex, age group, education level, and language regions were significant determinants of adherence to a cancer-protective lifestyle. Further actions at the governmental and individual levels promoting the adoption of a cancer-protective lifestyle are needed.