Disinfection by-products (DBPs) are formed during chlorination of drinking water and have been linked to increased cancer risk. This project aims to investigate the association of long-term exposure to DBP through drinking water with cancer incidence and mortality using data from the Swedish SIMPLER research infrastructure, which includes over 58,000 individuals on public drinking water. Building on previous findings that associated trihalomethane (THM) exposure with bladder and colorectal cancer, the study aims to assess associations with liver, kidney, breast, endometrial cancer, and malignant melanoma. The study will use a prospective cohort design and detailed exposure assessment based on a high-resolution database of over 108,000 water quality analyses from 52 public drinking water utilities. These data will be linked to participants’ residential histories from 1960 to 2018, enabling individual-level exposure estimates. Participants are categorized into high (≥15 µg/L), low (<15 µg/L), and zero exposure groups based on THM concentrations at baseline (1997), with annual updates to account for residential mobility. Utilities that do not use chemical disinfection serve as zero-exposure reference group. Cancer outcomes are identified through linkage to the Swedish Cancer Register and include site-specific cancers and overall cancer incidence and mortality. Survival analyses will be conducted, censoring individuals who move out of the study area or die from causes other than cancer. This study provides a unique opportunity to evaluate the carcinogenic potential of DBPs in drinking water and aims to inform public health policies regarding water disinfection practices and cancer prevention.