MicroRNA-145-5p (miR-145) has been reported to regulate multiple oncogenes and is considered a tumor suppressor. However, it remains unknown whether the level of plasma miR-145 can serve as a risk biomarker for future cancer. Using a population-based cohort ( = 1740) derived from the Trøndelag Health Study (HUNT), we investigated whether plasma miR-145 levels were associated with (1) first life-time cancer, (2) cancer stage at diagnosis, and (3) 2-year all-cause mortality after cancer diagnosis. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Our findings showed that individuals in the highest quartile of plasma miR-145 levels had a 44% increased risk of developing cancer compared to those in the lowest quartile, independent of age, sex, body mass index, or smoking status (HR 1.44, 95% CI 1.03-2.00 < 0.05). However, no association was observed between quartiles of miR-145 levels and the risk of being diagnosed with a metastatic cancer, or the risk of 2-year mortality after cancer diagnosis. Our findings suggest that high plasma miR-145 levels are associated with increased cancer risk without affecting the severity of the cancer at diagnosis or affecting the short-term prognosis.