We investigated the Asian lacquer-based surface coating of a historical Guqin named “Qiu Bo” collected in the Museum of Dr.Sun Yat-sen in Zhongshan, Guangdong Province, China. The instrument is believed to have been made in the studio of Prince Yi of the Ming Dynasty in Fuzhou, Jiangxi Province, and has been widely deemed as one of the four most treasured Guqin pieces in the Lingnan region. Multi-analytical measures, including optical cross-section microscopy, SEM-EDS, micro-Raman, O-PTIR and THM-Py-GC/MS, were used to identify the inorganic and organic materials for the surface coating and to reconstruct its lacquering techniques. The analytical results reveal two generations of layers with distinct materials and crafts. In the earlier generation, the ground layers were made of inorganic minerals and protein-non/semi-dyring oil binding media. In the later generation, the ground layers were made of deer antler or bone ashes bound with Asian lacquer-drying oil. These findings correspond to the instrument’s inscriptions indicating its fabrication in the Ming Dynasty in 1636 and its restoration in the Qing Dynasty in 1864. Laccol, a lacquer species, was discovered in the restoration layers using the ESCAPE database and the Excel worksheet developed by Getty Conservation Institute. This is the first reported case of laccol, primarily produced in Vietnam, used in Chinese domestic Guqin instruments. By combining scientific analyses and archival research on historical Guqin and lacquer art treatises such as Tai Gu Yi Yin, Xiu Shi Lu, etc., this study contributes to a better understanding of the craft for making the Guqin and the restoration traditions in pre-modern Guangdong. This knowledge could also benefit the conservation treatments of Guqin and other lacquer artworks.