Using submerged fermentation of the mycelium of Ganoderma lucidum, the medium composition and fermentation conditions were optimized based on the growth of mycelia and the inhibition ratio of tyrosinase. Meanwhile, metabolomics analysis of the fermentation broth by mass spectrometry was performed to determine the key whitening factors in the fermentation broth. The results showed that optimum culture conditions were: malt extract 2 g/mL, sucrose 1.72 g/mL, soybean meal powder 0.214 g/mL, yeast extract 0.1 g/mL, pH5, temperature 30 ℃, cultured at 6 d, 160 r/min. Under this condition, the inhibition rate of tyrosinase was reached 95.1%, indicating its optimal whitening effect. 212 metabolites including polysaccharides, triterpenes, nucleotides and amino acids were identified. Among them, polysaccharides and triterpenes were the major components with 26 and 30 species respectively. The content of G. lucidum polysaccharide in the fermentation broth was 24.8 mg/mL, and the content of triterpene was 55.7 μg/mL. Based on metabolomic data, the polysaccharides and triterpenes in fermentation broth were isolated and determined. The correlation between the content of polysaccharides and triterpenes in fermentation broth and the inhibitory activity of tyrosinase was analyzed in this study. The results showed that the triterpenoid content and tyrosinase inhibitory activity were positively correlated, but the content of polysaccharide was no obvious correlation and inhibit tyrosinase activity, suggesting that the main whitening factor in the fermented broth were triterpenes.