Background: Prostate cancer remains a significant cause of morbidity and mortality among black men. There is evidence of an increase in the disease burden in recent years. The role of trace elements like Zinc in the aetio-pathogenesis and possible disease prevention is still controversial. Objectives: The aim of this study is to identify the relationship between tissue zinc concentration and the occurrence of prostate cancer among men in Ile-Ife, Nigeria. It also aimed at identifying the relationship between the tissue zinc concentration and the disease severity (using the prostate specific antigen and gleason scores). Methodology: It was a prospective hospital-based comparative study carried out in the Urology unit of the Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, over a period of one year. Consecutive consenting men with histologically confirmed prostate cancer alongside age-matched controls were recruited and had big toe-nail clippings obtained for this study. The prostate specific antigen and Prostate histological gleason scores were also retrieved. Zinc concentration in the toe-nail was assayed using the Particle induced X-ray emission (PIXE) technique at the Centre for Energy and Research Development Laboratory, OAU Ile-Ife. Data Analysis: The data was entered and analysed using SPSS statistical software version 20. Univariate analyses were utilized to determine the sociodemographic data of the subjects, using percentages and means (with standard deviation). The independent T-test was employed to determine if there was any significant difference in toe-nail zinc concentration between the study groups using 0.05 level of significance (P < 0.05) with a 95% confidence interval. Pearson’s correlation was used to check the relationship between Zinc concentration and PSA/Gleason score. Results : Forty one men with PCa and forty one age-matched controls were recruited for this study. The PCa patients had a mean age of 72.83 ± 7.06 years while the controls had a mean age of 70.73 ±6.40 years. There was no statistically significant difference in age distribution between the two groups. Both groups had similar occupations and places of residence. The toe-nail Zinc concentration among PCa patients ranged from 38.4-594.6μg/g with a median and inter quartile range of 116.5 and 256.47 μg/g respectively while in the controls it ranged from 56.7 to 313.8μg/g with a median and inter-quartile range of 96.1 and 29.4 μg/g respectively. There was statistically significant higher toe-nail Zn concentration among Prostate cancer patients than controls (P= 0.028, t=2.28, df=40). The PSA values among the PCa group ranged from 12.0 to 177 ng/ml with a mean of 46.10 ± 40.62, median 34 ng/ml while in the control group ranged from 1.8 to 6.5 ng/ml with a mean of 3.88 ± 1.58. The Gleason scores in PCa patients ranged from 6 to 10 with a mode Gleason score of 8. There was a weak correlation between toe-nail Zn concentration and PSA though statistically insignificant (p=0.386). On the other hand, there was a weakly inverse relationship between the toe-nail Zn concentration and Gleason score. Conclusion: This study found a statistically significant higher toe-nail Zn concentration among men with PCa compared with age-matched controls in Ile-Ife. There was however no correlation between toe-nail Zn concentration and PSA or Gleason score. Keywords: Prostate cancer, Zinc, Particle-induced X-ray emission, Gleason score, Prostate specific antigen.