Background In the human body, volatile organic compounds (VOCs) are produced by different tissues then secreted in different body fluids and subsequently excreted. Here we explore a non-invasive method for the detection of liver, prostate and bladder cancers. Methods We recruited 140 cases. There were 31 hepatocellular carcinomas (HCC), 62 prostate carcinomas, 29 bladder carcinomas and 18 non-cancer cases. Male to female ratio was 5:1 and mean age was 72 years. Urinary VOCs were detected by applying the solid-phase microextraction (SPME) technique. Results The sensitivity for detection of HCC with normal alpha fetoprotein (AFP) was 68% (SE 0.06, 95% CI 0.54 to 0.81 and P <0.005). The VOCs sensitivity in the detection of HCC cases with raised AFP was 83%. (SE 0.05, 95% CI 0.73 to 0.93 and P<0.0001). The VOCs sensitivity for prostate cancer detection was 70% (SE 0.049, 95% CI 0.60 to 0.79 and P<0.0002) and sensitivity for bladder cancer detection was 81% (SE 0.052, 95% CI 0.70 to 0.91 and P<0.0001). Conclusions SPME urinary VOCs analysis was able to differentiate between controls and each of hepatocellular, prostate and bladder cancers. This suggests that urinary VOCs are cancer specific and could potentially be used as a diagnostic method.Creative Commons Attribution license.