Active surveillance is the preferred strategy for very low risk, low risk, and some favorable intermediate risk of prostate cancer. However, the current risk stratifications with initial prostate-specific antigen (iPSA) levels and Gleason scores at biopsy can underestimate the true oncologic threat. More precise predictors are required to avoid the overtreatment of prostate cancer. H19 single-nucleotide polymorphisms (SNPs) have been found to play crucial roles in numerous malignancies, but not yet in prostate cancer. This study assessed the clinicopathologic effects of H19 SNPs on prostate cancer to identify potential active surveillance candidates. A total of 579 patients with prostate cancer who underwent robot-assisted radical prostatectomy between 2012 and 2017 were recruited. The patients were grouped by iPSA levels, and five H19 SNPs were evaluated. Our results show that patients with an iPSA level of ≤7 ng/mL had increased an likelihood of having Gleason score and group grade upgrades after radical prostatectomy compared with patients with an iPSA level of >7 ng/mL. Moreover, patients with loci polymorphisms in either rs3024270 or rs3741219 had a significantly higher risk of perineural invasion (rs3024270: Odds ratio (OR) 2.76, 95% confidence interval (CI) 1.30–5.87, p = 0.01; rs3741219: OR 2.30, 95% CI 1.17–4.54, p = 0.018). In conclusion, our results suggested that H19 SNPs play a role in the perineural invasion of prostate cancer.