Background Long non‐coding RNA (lncRNA) H19 is involved in the carcinogenesis, progression, and metastasis of colorectal cancer (CRC). Recently, a few studies explored the relationship between lncRNA H19 gene rs2839698 polymorphism and CRC risk, but with conflicting findings. Materials and methods A case‐control study with 315 CRC cases and 441 controls was designed in a Chinese population. Genotyping was performed using PCR‐RFLP. Results It was found rs2839698 polymorphism was associated with a decreased risk of CRC (AA vs GG: OR, 0.73; 95% CI, 0.54‐0.98; P = .037; A vs G: OR, 0.78; 95% CI, 0.63‐0.96; P = .021). Stratified analyses indicated this positive association was also significant in the non‐smokers (AA vs GG: OR, 0.49; 95% CI, 0.25‐0.93; P = .029), non‐drinkers, those aged ≥ 60 years, and overweight individuals (BMI ≥ 24). In addition, rs2839698 polymorphism was also related to the lymph node metastasis (AA vs GG: OR, 0.43; 95% CI, 0.21‐0.88; P = .019) and tumor size (AA vs GG: OR, 0.42; 95% CI, 0.20‐0.88; P = .020) for patients with CRC. Conclusion To sum up, the lncRNA H19 gene rs2839698 polymorphism decreases the risk of CRC in Chinese individuals, especially among the non‐smokers, non‐drinkers, individuals aged ≥ 60 years, and overweight individuals (BMI ≥ 24). Thus, the lncRNA H19 gene rs2839698 polymorphism might be an important biomarker and diagnostic marker for predicting the susceptibility to CRC in Chinese Han population.

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