Cervical cancer is one of the cancers commonly found in the female reproductive system and is associated with obesity. However, the exact connection mechanisms remain unclear. Screening of key therapeutic targets and natural products with good antitumor activity has become a crucial strategy for cancer therapy. Cryptotanshinone is one of the main extracts of tanshinone, which has anti-inflammatory and anti-cancer properties. Key therapeutic targets and related low-toxicity natural active ingredients were identified as crucial components in cancer treatment strategies. Therefore, network pharmacology and cellular biology techniques were used to screen and validate key targets in obesity-related cervical cancer and to elucidate the mechanisms of its cryptotanshinone. The results indicated that C-X-C motif chemokine ligand 8 (CXCL8) might be modulated by cryptotanshinone. The knockdown of CXCL8 significantly reduced Hela cell viability to 15.29% ± 4.59% compared with the control group (p <
0.01), which consequently inhibited both cell proliferation and lipid droplet formation. Moreover, cryptotanshinone (20, 40, and 80 µM) significantly reduced CXCL8 expression and inhibited the NOD-like receptor signaling pathway in Hela cells compared with the control group (p <
0.01). Therefore, this study manifested that cryptotanshinone potentially played an important role in obesity-related cervical cancer. This study provided an important experimental basis for further exploring the pathogenesis and prevention of obesity-related cervical cancer.