The truncating mutations of RNF43 frequently occur in CRC, we aimed to clarify the relationship between RNF43 frameshift mutations and MS status, BRAF V600E mutation, distant metastasis, TNM stage and location of CRC. RNF43 frameshift mutations R117.fs and G659.fs and BRAF V600E mutation were detected in 392 sporadic CRC samples from our tissue bank. We integrated our original study with the TCGA database and five published datasets to analyse the relationship between RNF43 frameshift mutation and tumour location, distant metastasis, TNM stage and BRAF V600E mutation in 2396 CRC samples when controlling for MS status. RNF43 frameshift mutation was correlated with MSI-H (OR = 122.27) [31.82, 469.92], BRAF V600E mutation (OR = 7.92 [3.45, 18.18]), distant metastasis (OR = 0.30 [0.17, 0.53]), advanced TNM stage (OR = 0.34)[0.23, 0.51], and right colon site (OR = 8.32 [2.98, 23.22]). After controlling for the effect of MS status, there was no correlation of RNF43 frameshift mutation with distant metastasis (OR = 1.57 [0.75, 3.28]) and advanced TNM stages (OR = 0.98 [0.58, 1.67]), but RNF43 frameshift mutations still occur more frequently in right colon (OR = 2.58 [1.49, 4.47]) and with BRAF V600E mutation (OR = 1.94 [1.22, 3.10]). RNF43 frameshift mutations were related to distant metastasis and TNM-stage in an MS status-dependent manner, but they contributed to tumourigenesis in right-sided colon cancer independent of MS status.