Objective: Hand grip strength (HGS) could be taken as a biomarker for overall health of individual. While growing evidence suggests cesarean section (C-section) related to child health, few studies have assessed its effect on the overall health status of offspring. Design: Cross-sectional cohort study. Setting: UK Biobank cohort. Population: A population-based cohort consisting of 160,635 participants for left HGS and 160,651 for right HGS aged between 40 and 69. Methods: Regression analyses were conducted to test the associations between C-section and left HGS and right HGS. Then, genome-wide of environment interaction study (GWEIS) was conducted by PLINK 2.0 to identify loci with gene-environment (G×E) interaction effects, using C-section as an environmental factor. FUMA platform was used for functional gene set enrichment analysis of identified candidate genes. Main Outcome Measures: C-sections and hand grip strength. Results: The regression analyses showed significant associations (P <0.001) between C-section and left and right HGS. GWEIS detected 6 significant G×E interaction effects on left HGS, such as ADGRV1 gene, POLR3G gene, and WASL gene. 32 significant G×E interactions effects on right HGS were detected, such as APBB2 gene, and CRPPA gene. Comparing the analyses results of left HGS and right HGS, identified suggestive significant interactions between CLEC16A gene and C-section, such as rs80001954 (Pright = 5.21 × 10−8, Pleft = 1.22 × 10−7); rs117658390 (Pright = 5.43 × 10−8, Pleft = 1.09 × 10−7) and rs79479146 (Pright  = 5.45 × 10−8, Pleft  = 1.22 × 10−7). Gene set enrichment analyses reported 12 GO terms, such as GO_CENTRAL_NERVOUS_SYSTEM_DEVELOPMENT (adjusted P = 1.98 × 10−3), and GO_HEAD_DEVELOPMENT (adjusted P = 5.09 × 10−3). Conclusion: Our study holds potential for clarifying the functional relevance of C-section with HGS