PurposeTo examine the association of muscle-strengthening activities (MSA) and cancer mortality.MethodsWe pooled data from the 1998 to 2009 National Health Interview Survey (NHIS), which were linked to records in the National Death Index. Mortality follow-up was through 31 December 2011. Based on U.S. federal guidelines for physical activity, we dichotomized MSA and compared those who performed MSA twice a week or more to others with lower MSA. We also examined dose–response relationship of MSA frequency with cancer mortality. Hazard ratios (HR) from Cox regression were computed to estimate the association of MSA with the risk of cancer mortality. Mean follow-up was 7.9 years and the analysis sample size was 310,282.ResultsCovariate-adjusted results showed that meeting the MSA guideline was associated with a 19% lower risk of cancer mortality (HR 0.81, 95% CI 0.73, 0.90). We found no evidence of a dose–response relationship between the frequency of performing MSA and cancer mortality.ConclusionAdhering to the U.S. federal guideline for MSA is associated with lower cancer mortality. Public health programs and policy for cancer prevention and control should promote MSA to further reduce cancer mortality.