Abstract Background There is an association between increased dietary sodium intake and the risk of stomach cancer. Lowering dietary sodium intake with sodium-reduced potassium-enriched salt substitutes may reduce this risk. To evaluate the effects of sodium-reduced potassium-enriched salt substitutes on the risk of stomach cancer and other types of cancer. Methods The primary analyses of the Salt Substitute and Stroke Study (SSaSS) defined the effects of sodium-reduced potassium-enriched salt substitutes compared to regular salt on the risk of stroke. This post-hoc investigation explored effects on stomach and other cancers. SSaSS was an open-label, cluster randomised controlled trial done in 600 Chinese villages among 20,996 participants. Villages were assigned at random in a 1:1 ratio to receive sodium-reduced potassium-enriched salt substitutes or continue regular salt use. Fatal and hospitalised cancer events were identified through direct face-to-face follow-up and record linkage, with adjudication of fatal, but not non-fatal events. Results During a mean follow-up of 4.7 years, there were 1040 cancer events (507 fatal, 533 non-fatal) recorded. There were 212 stomach cancers, 725 other cancers, and 103 cancers with an unknown primary site. There was a trend toward but not a significant effect of randomised treatment on total stomach cancer (rate ratio (RR) 0.77, 95% confidence interval (CI) 0.54 to 1.08). The RR for adjudicated fatal stomach cancer was 0.66 (95% CI 0.44 to 1.00) compared to 0.88 (95% CI 0.56 to 1.37) for unadjudicated non-fatal stomach cancer. There was no detectable effect on total cancer at any site (RR 0.94, 95% CI 0.81 to 1.08), adjudicated fatal cancer at any site (RR 0.85, 95% CI 0.69 to 1.05), or unadjudicated non-fatal cancer at any site (RR 1.04, 95% CI 0.88 to 1.23). Conclusions There was no effect of sodium-reduced potassium-enriched salt substitutes on stomach cancer or other cancer types detected. Trends toward protection against fatal and non-fatal stomach cancer align with the observational epidemiology and warrant further investigation. Trial registration This trial was registered in ClinicalTrials.gov as NCT02092090.