With the increasingly serious burden of osteoarthritis (OA) on modern society, it is urgent to propose novel diagnostic biomarkers and differentiation models for OA. 7-methylguanosine (m7G), as one of the most common base modification forms in post transcriptional regulation, through which the seventh position N of guanine (G) of messenger RNA is modified by methyl under the action of methyltransferase; it has been found that it plays a crucial role in different diseases. Therefore, we explored the relationship between OA and m7G. Based on the expression level of 18 m7G-related regulators, we identified nine significant regulators. Then, via a series of methods of machine learning, such as support vector machine recursive feature elimination, random forest and lasso-cox regression analysis, a total of four significant regulators were further identified (DCP2, EIF4E2, LARP1 and SNUPN). Additionally, according to the expression level of the above four regulators, two different m7G-related clusters were divided via consensus cluster analysis. Furthermore, via immune infiltration, differential expression analysis and enrichment analysis, we explored the characteristic of the above two different clusters. An m7G-related scoring model was constructed via the PCA algorithm. Meanwhile, there was a different immune status and correlation for immune checkpoint inhibitors between the above two clusters. The expression difference of the above four regulators was verified via real-time quantitative polymerase chain reaction. Overall, a total of four biomarkers were identified and two different m7G-related subsets of OA with different immune microenvironment were obtained. Meanwhile, the construction of m7G-related Scoring model may provide some new strategies and insights for the therapy and diagnosis of OA patients.