* Age \>= 18 years. * HCC diagnosis confirmed by histology/cytology or clinically by American Association for Study of Liver Diseases (AASLD) criteria in cirrhotic patients. * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 * Locally advanced, metastatic, or unresectable disease. * Child Pugh class A. * Barcelona clinic liver cancer (BCLC) stage B (not amenable to liver directed therapy) or stage C. * Prior treatment with atezolizumab and bevacizumab combination with radiographic progression that necessitates change in treatment per treating physician. Patients with rapid progression on atezolizumab and bevacizumab (defined as patients who progressed radiographically in the first restaging scan that necessitates change in treatment) are excluded. * Washout period \>= 4 weeks prior to registration is required since last atezolizumab and bevacizumab dose. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. (Form is available on the Academic and Community Cancer Research United \[ACCRU\] website). * Absolute neutrophil count (ANC) \>= 1000/mm \^ 3 (obtained =\< 28 days prior to registration). * Platelet count \>= 60,000/mm\^3 (obtained =\< 28 days prior to registration). * Hemoglobin \>= 8.5 g/dL (obtained =\< 28 days prior to registration). * Total bilirubin =\< 3 x upper limit of normal (ULN) (obtained =\< 28 days prior to registration). * Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 5 x ULN (obtained =\< 28 days prior to registration). * International normalized ratio (INR) =\< 2.3 or Prothrombin time (PT) =\< 6 seconds above control OR if patient is receiving anticoagulant therapy and INR is within target range of therapy creatinine =\< 1.5x ULN (obtained =\< 28 days prior to registration). * Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only. * Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Provide informed written consent =\< 28 days prior to registration. * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study). * Note: During the active monitoring phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up. * Willing to provide mandatory tissue specimens and blood specimens for correlative research purposes.